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Sample records for dual immunosuppressive therapy

  1. Osteoporosis following heart transplantation and immunosuppressive therapy.

    Science.gov (United States)

    Löfdahl, Eveline; Rådegran, Göran

    2017-08-12

    Heart transplantation (HT) remains the ultimate final therapy for patients with end-stage heart failure, who despite optimal medical and surgical treatments exhibit severe symptoms. To prevent rejection of the transplanted organ, HT patients require life-long immunosuppressive therapy. The goal of the immunosuppression is to minimise the risk of immune-mediated graft rejection, while avoiding clinical side-effects. Current immunosuppressive agents have yielded good survival outcome, however, complications of the immunosuppressive therapy, such as impaired bone strength and increased fracture risk, are common among HT patients rendering increased morbidity and mortality rates. The main aim of the present review was to summarise current knowledge on bone strength impairment after HT and concomitant immunosuppressive therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Immunosuppressive effects of silicon phthalocyanine photodynamic therapy.

    Science.gov (United States)

    Reddan, J C; Anderson, C Y; Xu, H; Hrabovsky, S; Freye, K; Fairchild, R; Tubesing, K A; Elmets, C A

    1999-07-01

    The purpose of this study was to determine if silicon phthalocyanine 4 (Pc 4), a second-generation photosensitizer being evaluated for the photodynamic therapy (PDT) of solid tumors, was immunosuppressive. Mice treated with Pc 4 PDT 3 days before dinitrofluorobenzene sensitization showed significant suppression of their cell-mediated immune response when compared to mice that were not exposed to PDT. The response was dose dependent, required both Pc 4 and light and occurred at a skin site remote from that exposed to the laser. The immunosuppression could not be reversed by in vivo pre-treatment of mice with antibodies to tumor necrosis factor-alpha or interleukin-10. These results provide evidence that induction of cell-mediated immunity is suppressed after Pc 4 PDT. Strategies that prevent PDT-mediated immunosuppression may therefore enhance the efficacy of this therapeutic modality.

  3. Nail changes in female pemphigus vulgaris patients on immunosuppressive therapy

    OpenAIRE

    M.M. El-Komy, MD; D.M. Abdel Halim, MD; N. Samir, MD; R.A. Hegazy, MD; H.I. Gawdat, MD; S.A. Shoeb, MD

    2015-01-01

    Background: Pemphigus vulgaris (PV) patients receiving immunosuppressive therapy may develop nail alterations resulting from infection, skin disorder, or drug regimen. Objective: This study aims to describe nail changes in PV female patients receiving immunosuppressive therapy and to report the frequency of associated fungal and bacterial growth in the patients’ nails. Methods: Twenty-five female PV patients who had at least one acquired finger or toenail abnormality and had been admini...

  4. New Immunosuppressive Therapies in Uveitis Treatment

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    Salvador Mérida

    2015-08-01

    Full Text Available Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines.

  5. New Immunosuppressive Therapies in Uveitis Treatment

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    Mérida, Salvador; Palacios, Elena; Navea, Amparo; Bosch-Morell, Francisco

    2015-01-01

    Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines. PMID:26270662

  6. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans.

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    Thanos, S M; Halliday, G M; Damian, D L

    2012-09-01

    The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  7. [Tapering and termination of immunosuppressive therapy : Systemic lupus erythematosus].

    Science.gov (United States)

    Aringer, M; Leuchten, N; Fischer-Betz, R

    2017-02-01

    Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

  8. Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

    Science.gov (United States)

    Nath, Avindra

    2016-01-01

    Opinion statement The first critical step in the appropriate treatment of neurological infectious disease accompanying immunosuppressive states or immunomodulatory medication is to properly identify the offending organism. Broadly immunosuppressive conditions will predispose to both common and uncommon infectious diseases. There are substantial differences between neurological infectious disorders complicating disturbances of the innate immunity (neutrophils, monocytes and macrophages) and those due to abnormal adaptive immunity (humoral and cellular immunity). Similarly, there are differences in the types of infections with impaired humoral immunity compared to disturbed cellular immunity and between T- and B-cell disorders. HIV/AIDS has been a model of acquired immunosuppression and the nature of opportunistic infections with which it has been associated has been well characterized and generally correlates well with the degree of CD4 lymphopenia. Increasingly, immunotherapies target specific components of the immune system, such as an adhesion molecule or its ligand or surface receptors on a special class of cells. These targeted perturbations of the immune system increase the risk of particular infectious diseases. For instance, natalizumab, an α4β1 integrin inhibitor that is highly effective in multiple sclerosis, increases the risk of progressive multifocal leukoencephalopathy for reasons that still remain unclear. It is likely that other therapies that result in a disruption of a specific component of the immune system will be associated with other unique opportunistic infections. The risk of multiple simultaneous neurological infections in the immunosuppressed host must always be considered, particularly with a failure to respond to a therapeutic regimen. With respect to appropriate and effective therapy, diagnostic accuracy assumes primacy, but occasionally broad spectrum therapy is necessitated. For a number of opportunistic infectious disorders

  9. COMPARATIVE STUDY OF PULSE THERAPY WITH DAILY IMMUNOSUPPRESSIVE THERAPY IN STEROID RESPONSIVE DERMATOSIS

    OpenAIRE

    Naseem Begum , SwathiBurla, Bhavika

    2015-01-01

    Background: Pemphigus, scleroderma and SLE are diseases of unknown etiology for which no specific treatment is effective. The introduction of corticosteroids and immunosuppressive drugs reduced the mortality rate. Objectives: To correlate signs and symptoms and incidence of adverse effects in patients with steroid responsive dermatosis before and during DCP therapy and daily immunosuppressive therapy. Material and Methods: 100 patients were enrolled in this study. They are divided into 2 grou...

  10. Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy

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    Ooka, Kohtaro; Lim, Joseph K.

    2016-01-01

    Abstract With 185 million people chronically infected globally, hepatitis C is a leading bloodborne infection. All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable. However, trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation. Yet, these patients—most often suffering from malignancy or autoimmune diseases—could stand to benefit from these treatments. In this study, we systematically review the literature on the treatment of hepatitis C in these neglected populations. Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically. Our systematic review produced 2273 unique works, of which 56 met our inclusion criteria and were used in our review. The quality of data was low; only 3 of the 56 studies were randomized controlled trials. Sustained virologic response was reported sporadically. Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals. Severe adverse effects and death were rare. Data on all-oral regimens were sparse, but in the most robust study, rates of sustained virologic response were again comparable to immunocompetent individuals (40/41). Efficacy and safety of interferon-containing regimens and all-oral regimens were similar to rates in immunocompetent individuals; however, there were few interventional trials. The large number of case reports and case series makes conclusions vulnerable to publication bias. While firm conclusions are challenging, given the dearth of high-quality studies, our results demonstrate that antiviral therapy can be safe and effective. The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects. Preliminary data reveal that these regimens may confer such benefits in

  11. Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

    LENUS (Irish Health Repository)

    Gabardi, Steven

    2011-09-01

    To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.

  12. [A case of cryptococcal meningitis with nephrotic syndrome and renal insufficiency under immunosuppressive therapy].

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    Tsuchida, Hiroki; Ichikawa, Daisuke; Shima, Yoshinori; Yasuda, Takashi; Sato, Takeo; Kimura, Kenjiro

    2007-01-01

    A 76 year-old woman was admitted to our hospital because of pyrexia and fatigue. One year earlier, she was diagnosed as nephrotic syndrome(NS) caused by focal segmental glomerulosclerosis and immunosuppressive therapy was started with marked amelioration of proteinuria. Thereafter, her renal function worsened, but only supportive treatment was continued. After admission, a cerebrospinal fluid (CSF) examination revealed Cryptococcus neoformans (C. neoformans) by india ink staining and a subsequent CSF culture confirmed C. neoformans infection. Accordingly, we made the diagnosis of cryptococcal meningitis and immediately started multiple anti fungal drugs with dosage modification according to her impaired renal function. Immunosuppressive therapy for NS was temporarily terminated. The inflammatory signs and symptoms soon were markedly improved, but the anti cryptococcal antibody titer in the serum and CSF remained high. Immunosuppressive therapy was started again at a low dosage because urinary protein had increased again. One hundred and eight days from admission, she was discharged with a regimen of multiple anti fungal drugs. Proteinuria and renal insufficiency was almost stable during hospitalization. Most fungal infection develops in patients in an immunosuppressive state induced by immunosuppressive drugs, HIV infection and so on. Patients with NS are frequently in an immunosuppressive state because of urinary loss of immunoglobulins and the use of immunosuppressive drugs. Therefore, it should be remembered that patients with NS are at a high risk of suffering from fungal infection.

  13. Adherence to immunosuppressive therapy following liver transplantation: an integrative review.

    Science.gov (United States)

    Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

    2016-08-29

    to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. investigar as evidências disponíveis na literatura sobre a não adesão à terapêutica imunossupressora entre pacientes submetidos ao transplante de fígado. revisão integrativa da literatura, que incluiu investigações cuja amostra era composta por pacientes com idade igual ou superior a 18 anos, submetidos a transplante de fígado. Excluíram-se as que continham pacientes submetidos a transplantes de múltiplos órgãos. Para a seleção dos artigos foram consultadas as bases Medline/Pubmed, CINAHL, LILACS, Scopus e Embase. O período de busca determinado correspondeu à data inicial de indexação das

  14. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

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    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  15. Combinatorial delivery of immunosuppressive factors to dendritic cells using dual-sized microspheres.

    Science.gov (United States)

    Lewis, Jamal S; Roche, Chris; Zhang, Ying; Brusko, Todd M; Wasserfall, Clive H; Atkinson, Mark; Clare-Salzler, Michael J; Keselowsky, Benjamin G

    2014-05-07

    Microparticulate systems are beginning to show promise for delivery of modulatory agents for immunotherapeutic applications which modulate dendritic cell (DC) functions. Co-administration of multiple factors is an emerging theme in immune modulation which may prove beneficial in this setting. Herein, we demonstrate that localized, controlled delivery of multiple factors can be accomplished through poly (lactic-co-glycolic acid) (PLGA) microparticle systems fabricated in two size classes of phagocytosable and unphagocytosable microparticles (MPs). The immunosuppressive ability of combinatorial multi-factor dual MP systems was evaluated by investigating effects on DC maturation, DC resistance to LPS-mediated maturation and proliferation of allogeneic T cells in a mixed lymphocyte reaction. Phagocytosable MPs (~2 μm) were fabricated encapsulating either rapamycin (RAPA) or all-trans retinoic acid (RA), and unphagocytosable MPs (~30 μm) were fabricated encapsulating either transforming growth factor beta-1 (TGF-β1) or interleukin-10 (IL-10). Combinations of these MP classes reduced expression of stimulatory/costimulatory molecules (MHC-II, CD80 and CD86) in comparison to iDC and soluble controls, but not necessarily to single factor MPs. Dual MP-treated DCs resisted LPS-mediated activation, in a manner driven by the single factor phagocytosable MPs used. Dendritic cells treated with dual MP systems suppressed allogeneic T cell proliferation, generally demonstrating greater suppression by combination MPs than single factor formulations, particularly for the RA/IL-10 MPs. This work demonstrates feasibility of simultaneous targeted delivery of immunomodulatory factors to cell surface receptors and intracellular locations, and indicates that a combinatorial approach can boost immunoregulatory responses for therapeutic application in autoimmunity and transplantation.

  16. Immunosuppressive therapy for transplant-ineligible aplastic anemia patients.

    Science.gov (United States)

    Schrezenmeier, Hubert; Körper, Sixten; Höchsmann, Britta

    2015-02-01

    Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials.

  17. Persistent Hypotony Associated with Immunosuppressive Therapy in Glaucoma Drainage Implant Surgery

    Science.gov (United States)

    Duch, Susana; Milla, Elena; Stirbu, Oana; Andreu, David

    2016-01-01

    Purpose To describe the histopathology of non-valved implant capsules in three cases of persistent postoperative hypotony after the restrictive tube ligature was released in patients receiving immunosuppressive therapy. Observations The macroscopic appearance of the capsules 3 and 4 months postoperatively was immature and loose. Microscopic examination disclosed extremely irregular thin tissue, with thicknesses ranging from 0.02 to 0.6 mm, depending on the capsular location studied. Withdrawal of immunosuppressive therapy did not facilitate rebuilding of new capsules. Replacement with a valved implant device was necessary in two cases; the third case recovered with tapering of prednisone. Conclusions and Importance The use of chronic systemic immunosuppressive therapy might interfere with capsular formation around the plates of drainage devices inducing persistent hypotony. In these cases, the use of valved implants might be safer.

  18. Less is more: the detrimental consequences of immunosuppressive therapy in the treatment of type-1 diabetes.

    Science.gov (United States)

    Askenasy, Nadir

    2015-01-01

    The prevalent current approach to type 1 diabetes (T1D) is the abrogation of pathogenic potential by immunosuppressive therapy, an intuitive approach aiming to slow down disease progression by the reduction of pathogenic burden. In spite of promising initial results in rodent models, there has been little efficacy of most lymphoreductive strategies in human subjects. Our analysis suggests that lymphopenia is the common denominator of ineffective immunosuppressive therapies: Immune rebound from lymphopenia is associated per se with increased susceptibility to immune reactivity, including relapse of autoimmunity. In addition, immune homeostasis and self-tolerance are not restored. These considerations raise the following question: What is the allowed degree of immunosuppressive therapy that does not elicit recurrent autoimmunity. More effective therapeutic strategies include targeted deletion of pathogenic cells, preferably in the pancreatic islets and regional lymphatics using selective T cell activation markers, re-education and remodeling of effector responses.

  19. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-12-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972.

  20. Renaissance of immunosuppressive therapy in the new millennium.

    Science.gov (United States)

    Kahan, B D

    1998-08-01

    Immunosuppression in the next millennium will be based not merely on the survival of the patient and his graft, but more importantly on regimens that optimize the "Three C's": Co-morbidity, Cost, and Convenience. To meet these goals, the field of transplantation urgently requires new technologies: both new scientific tools of drug design, testing, and implementation, and informational tools including a categorical database and theoretical models to answer specific therapeutic questions. Just as the Renaissance marked a renewed interest in man himself after an age of Medieval spiritualism, so too will transplantation need to address the unique concerns of each patient to achieve an optimal outcome that includes self-reliance and the desired "texture of life." In weaving our tapestry for the 21st century, we must meet these challenges not merely with the 20th century tools at hand but with a strategic vision that searches for, readily adopts, and effectively harnesses unique technology.

  1. Intestinal strongyloidiasis in a psoriatic patient following immunosuppressive therapy: Seeing the unforeseen

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    Poongodi Lakshmi Santhana Kumaraswamy

    2016-01-01

    Full Text Available Strongyloides stercoralis , an intestinal nematode, has a complicated life cycle. Mostly asymptomatic, if symptomatic it has nonspecific, transient clinical manifestations. The two aggressive forms of the disease are: Hyperinfection syndrome (HS or disseminated syndrome (DS. Several risk factors have been associated with strongyloidiasis including immunosuppressive therapy, human immunodeficiency virus (HIV infection, diabetes, alcoholism, tuberculosis, impaired bowel motility, surgically created intestinal blind loops, chronic obstructive pulmonary disease, and chronic renal failure. We describe a case of intestinal strongyloidiasis in a psoriatic patient treated with immunosuppressive therapy.

  2. Immunosuppressive therapy induced coronary vasospasm and acute myocardial infarction in a patient undergoing new renal transplantation

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    Akturk, Ibrahim Faruk; Yalcin, Ahmet Arif; Celik, Omer; Oner, Ender

    2015-01-01

    Immunosuppressant agents such as calcineurin inhibitors (CNI) used after solid organ transplantation may cause endothelial dysfunction, and coronary and renal arterial vasospasm. We report a patient presenting acute ST segment elevation myocardial infarction (STEMI) at the second week of renal transplantation. In the case of STEMI in patients with solid organ transplants under immunosuppressive therapy with CNI, coronary vasospasm associated with these drugs should be kept in mind before starting any interventional procedure. High dose nitroglycerine may immediately resolve tacrolimus or cyclosporine A induced coronary vasospasm. Calcium channel blockers should immediately be added to treatment because of the short half-life of nitroglycerine. PMID:26161107

  3. Giant Condyloma Acuminata in Indonesian Females with SLE under Immunosuppressant and Steroid Therapy

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    Andhika Rachman

    2016-01-01

    Full Text Available Introduction. Immunosuppressant and steroid therapy in systemic lupus erythematosus (SLE increases the risk of human papillomavirus (HPV infections, one of which is giant condyloma acuminata (GCA. To our knowledge, there is no report evaluating the correlation between immunosuppressive and steroid therapy in patients with SLE and the prevalence of GCA. Case Report. A 42-year-old female was diagnosed with SLE a year ago and has been treated with steroids and immunosuppressive drugs. In the last few months she presented GCA involving the genital area recurring almost every two months. Type 6 and 11 HPVs were identified in vulva, vagina, and cervix. Methods. PubMed, EBSCO, and Cochrane Library literature were searched from inception to July 2015. Authors screened all titles and abstracts and read full text article, and two case-control studies were found relevant. Results. SLE patients in both studies were under immunosuppressive and steroid therapy. Condyloma acuminata was diagnosed at 108 months (latest and 1 month (earliest after SLE. Type 6, 11, 16, 42, and oncogenic group of HPV were identified. Conclusions. GCA is a type of HPV infection seldom observed in SLE patients. Therefore, their correlation is still unclear. Period of time since SLE was diagnosed and GCA varies from months to years. A more thorough physical and laboratory examination leading to HPV and other infectious disease is recommended.

  4. Giant Condyloma Acuminata in Indonesian Females with SLE under Immunosuppressant and Steroid Therapy

    Science.gov (United States)

    2016-01-01

    Introduction. Immunosuppressant and steroid therapy in systemic lupus erythematosus (SLE) increases the risk of human papillomavirus (HPV) infections, one of which is giant condyloma acuminata (GCA). To our knowledge, there is no report evaluating the correlation between immunosuppressive and steroid therapy in patients with SLE and the prevalence of GCA. Case Report. A 42-year-old female was diagnosed with SLE a year ago and has been treated with steroids and immunosuppressive drugs. In the last few months she presented GCA involving the genital area recurring almost every two months. Type 6 and 11 HPVs were identified in vulva, vagina, and cervix. Methods. PubMed, EBSCO, and Cochrane Library literature were searched from inception to July 2015. Authors screened all titles and abstracts and read full text article, and two case-control studies were found relevant. Results. SLE patients in both studies were under immunosuppressive and steroid therapy. Condyloma acuminata was diagnosed at 108 months (latest) and 1 month (earliest) after SLE. Type 6, 11, 16, 42, and oncogenic group of HPV were identified. Conclusions. GCA is a type of HPV infection seldom observed in SLE patients. Therefore, their correlation is still unclear. Period of time since SLE was diagnosed and GCA varies from months to years. A more thorough physical and laboratory examination leading to HPV and other infectious disease is recommended. PMID:27843658

  5. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

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    Weigel, S.; Kloska, S.; Freund, M. [Dept. of Clinical Radiology, Univ. Hospital of Muenster, Muenster (Germany); Kehl, H.G. [Dept. of Pediatric Cardiology, Univ. Hospital of Muenster, Muenster (Germany)

    2003-12-01

    A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

  6. Immunosuppressive therapy in patients with aplastic anemia: a single-center retrospective study.

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    Hasan Jalaeikhoo

    Full Text Available Aplastic anemia (AA is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.Patients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA were treated with cyclosporine (CsA and danazol while patients with severe AA (SAA as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.Among the 63 studied patients, 29 (46% had NSAA and 34 (54% had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01. The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.This long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.

  7. Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment.

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    Arina, Ainhoa; Corrales, Leticia; Bronte, Vincenzo

    2016-02-01

    Immune response to tumors can be successfully oriented for therapeutic purposes, as shown by the clinical efficacy of checkpoint blockade in extending the survival of patients with certain solid and hematologic neoplasms. Nonetheless, numerous patients do not benefit from these new treatments. Tumor-specific CD8(+) T lymphocytes, either endogenously revived by checkpoint interference or adoptively transferred after in vitro expansion and retargeting, can be extremely efficient in controlling metastatic disease but have to overcome a number of restraints imposed by growing tumors. This immune escape relies on a profound modification of the tumor environment, which is rendered less permissive to lymphocyte arrival, persistence, and functional activity. We review here emerging findings on the main negative circuits limiting the efficacy of cancer immunotherapy, as well as novel and conventional approaches that can translate into rational combination therapies.

  8. Recombinant Human Thrombopoietin Treatment Promotes Hematopoiesis Recovery in Patients with Severe Aplastic Anemia Receiving Immunosuppressive Therapy

    OpenAIRE

    2015-01-01

    Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive therapy (IST). Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000 U, subcutaneously, three times a week). rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, b...

  9. Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation

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    Catić-Đorđević Aleksandra

    2017-01-01

    Full Text Available Immunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection as well as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients’ quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized. Therapeutic drug monitoring (TDM for immunosuppressive drugs is an essential, but at the same time insufficient tool due to low predictability of drug exposition and marked pharmacokinetic variability. Parallel therapeutic, biochemical and clinical monitoring may successfully optimize and individualize therapy for transplanted recipients, providing optimal medical outcomes. Modern pharmacotherapy management should include new biomarkers with better sensitivity and specificity that can identify early cell damage. The aim of this study was to point out the importance of finding new biomarkers that would enable early detection of adverse drug events and cell damage in organ transplant recipients. We wanted to confirm the importance of routine biochemical monitoring in improving the safety of immunosuppressive treatment.

  10. Clinical observation of treating 62 patients with severe aplastic anemia failing in immunosuppressive therapy by integrative medicine

    Institute of Scientific and Technical Information of China (English)

    苏尔云

    2013-01-01

    Objective To explore treatment methods for patients with severe aplastic anemia(SAA) failing in immunosuppressive therapy(IST). Methods Totally 62 SAA patients failing in IST were treated by integrative medicine(IM).

  11. Is immunosuppressive therapy the anchor treatment to achieve remission in systemic sclerosis?

    Science.gov (United States)

    Cappelli, Susanna; Bellando-Randone, Silvia; Guiducci, Serena; Matucci-Cerinic, Marco

    2014-06-01

    Since activation of the immune system and a perivascular infiltrate of inflammatory cells are key features of SSc, immunosuppression has long been considered to be an anchor treatment. Non-selective immunosuppression remains central to the treatment of interstitial lung disease (ILD) and skin involvement, with CYC most widely used to obtain remission. The use of MTX as a first-line agent may be considered in the presence of skin involvement without ILD. More recently, MMF has shown encouraging results in observational studies, but still needs more formal evaluation to verify if it can be considered an alternative drug to CYC or a maintenance agent such as AZA. Rituximab has provided promising results in small open-label studies and other novel therapies targeting specific molecular and cellular targets are under evaluation. Patients with rapidly progressing diffuse cutaneous SSc should be evaluated for haematopoietic stem cell transplantation.

  12. Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy.

    Science.gov (United States)

    Gonzalez, Stevan A; Perrillo, Robert P

    2016-06-01

    Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder.

  13. Successful Late Conversion to Mycophenolate Mofetil and Prednisone Immunosuppression Therapy in a Renal Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Iqbal A

    2000-01-01

    Full Text Available A 35-year old male patient developed elevated transaminases about an year after cadaveric donor renal transplantation maintained on triple immunosuppression therapy. Azathioprine was discontinued and the liver enzymes normalized. Three years later, he showed evidence of cyclosporin (CyA nephrotoxicity as well as sclerosing cholangitis. The dose of CyA was therefore reduced. This was followed shortly by deterioration of his renal function and mycophenolate mofetil (MMF (3 gm daily was therefore introduced. He developed intractable diarrhea, which improved on reducing the dose of MMF to 2 gm per day. Eventually, the patient seemed to stabilize on low dose CyA and prednisone (Pred along with 2 gm of MMF. Four months later, the patient discontinued CyA on his own but continued with MMF and Pred. Over the following two years, his renal functions have remained stable with serum creatinine of around 120 µmol/L, despite the low immunosuppression being administered.

  14. Immunosuppressive therapy exacerbates autoimmunity in NOD mice and diminishes the protective activity of regulatory T cells.

    Science.gov (United States)

    Kaminitz, Ayelet; Mizrahi, Keren; Yaniv, Isaac; Stein, Jerry; Askenasy, Nadir

    2010-09-01

    Mounting evidence indicates that immunosuppressive therapy and autologous bone marrow transplantation are relatively inefficient approaches to treat autoimmune diabetes. In this study we assessed the impact of immunosuppression on inflammatory insulitis in NOD mice, and the effect of radiation on immunomodulation mediated by adoptive transfer of various cell subsets. Sublethal radiation of NOD females at the age of 14 weeks (onset of hyperglycemia) delayed the onset of hyperglycemia, however two thirds of the mice became diabetic. Adoptive transfer of splenocytes into irradiated NON and NOD mice precipitated disease onset despite increased contents of CD25(+)FoxP3(+) T cells in the pancreas and regional lymphatics. Similar phenotypic changes were observed when CD25(+) T cells were infused after radiation, which also delayed disease onset without affecting its incidence. Importantly, irradiation increased the susceptibility to diabetes in NOD and NON mice (71-84%) as compared to immunomodulation with splenocytes and CD25(+) T cells in naïve recipients (44-50%). Although irradiation had significant and durable influence on pancreatic infiltrates and the fractions of functional CD25(+)FoxP3(+) Treg cells were elevated by adoptive cell transfer, this approach conferred no protection from disease progression. Irradiation was ineffective both in debulking of pathogenic clones and in restoring immune homeostasis, and the consequent homeostatic expansion evolves as an unfavorable factor in attempts to restore self-tolerance and might even provoke uncontrolled proliferation of pathogenic clones. The obstacles imposed by immunosuppression on abrogation of autoimmune insulitis require replacement of non-specific immunosuppressive therapy by selective immunomodulation that does not cause lymphopenia.

  15. Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

    Science.gov (United States)

    Pranteda, G; Carlesimo, M; Bottoni, U; Di Napoli, A; Muscianese, M; Pimpinelli, F; Cordiali, P; Laganà, B; Pranteda, G; Di Carlo, A

    2014-01-01

    A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated.

  16. Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2014-12-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Berthold Klein,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch11Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyObjective: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR containing immunosuppressive regimen.Methods: A total of 381 patients (age ≥18 years receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA and azathioprine (AZA was replaced by CsA and mycophenolate mofetil (MMF in 2001 and by tacrolimus (TAC and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus were applied since 2003.Results: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total. Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%, 56 patients with noncutaneous malignancy only (14.7%, and 16 patients with both cutaneous and noncutaneous malignancy (4.2%. Statistically significant

  17. Systematic review on the effectiveness of immunosuppressants and biological therapies in the treatment of autoimmune posterior uveitis.

    Science.gov (United States)

    Pato, Esperanza; Muñoz-Fernández, Santiago; Francisco, Félix; Abad, Miguel A; Maese, Jesús; Ortiz, Ana; Carmona, Loreto

    2011-02-01

    To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic arthritis, and macular edema. Systematic review. We conducted a sensitive literature search in Medline (from 1961) and EMBASE (from 1980) until October 2007. Selection criteria were as follows: (1) population: autoimmune posterior uveitis, chronic anterior uveitis in juvenile idiopathic arthritis, and macular edema; (2) intervention: immunosuppressive and biologic therapies; (3) outcomes: visual acuity, Tyndall, vitreous haze, macular edema, pars planitis, and retinal vasculitis. There were no limitations regarding study design. The quality of each study was evaluated using the Jadad's scale and Oxford Levels of Evidence. Two hundred sixty-five articles were selected for detailed review of the 4235 found in the initial search: 128 records were on immunosuppressants, 105 on biological therapies, and 32 on macular edema. Overall, both the immunosuppressive and the biologic therapies appeared effective in the treatment of autoimmune posterior uveitis, except for daclizumab in uveitis related to Behçet's disease, and for etanercept in any uveitis. In the treatment of macular edema, the drugs tested were also effective. Based on the evidence collated, immunosuppressants and biological therapies (except for daclizumab in Behçet and etanercept) may be effective in autoimmune uveitis and macular edema. No superiority may be inferred from this review. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Association of anti-PLA(2)R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy

    NARCIS (Netherlands)

    Bech, A.P.; Hofstra, J.M.; Brenchley, P.E.; Wetzels, J.F.

    2014-01-01

    BACKGROUND: The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome

  19. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts.

    Science.gov (United States)

    Swijnenburg, Rutger-Jan; Schrepfer, Sonja; Govaert, Johannes A; Cao, Feng; Ransohoff, Katie; Sheikh, Ahmad Y; Haddad, Munif; Connolly, Andrew J; Davis, Mark M; Robbins, Robert C; Wu, Joseph C

    2008-09-02

    Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4(+) T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus therapies significantly prolongs survival of hESCs for up to 28 days. Taken together, these data suggest that hESCs are immunogenic, trigger both cellular and humoral-mediated pathways, and, as a result, are rapidly rejected in xenogeneic hosts. This process can be mitigated by a combined immunosuppressive regimen as assessed by molecular imaging approaches.

  20. Very late relapse of PTLD 10 yrs after allogeneic HSCT and nine yrs after stopping immunosuppressive therapy

    DEFF Research Database (Denmark)

    Helgestad, Jon; Rosthøj, Steen; Pedersen, Morten Høgild

    2014-01-01

    the fever settled, the PET scan normalized, and the M-component disappeared. Without any ongoing immunosuppressive therapy, PTLD relapsed nine yr later with large intra-abdominal lymph node masses causing ureteric obstruction with bilateral hydronephrosis. Pathological features were identical to the primary...

  1. Dual antiplatelet therapy use by Canadian cardiac surgeons.

    Science.gov (United States)

    Yanagawa, Bobby; Ruel, Marc; Bonneau, Christopher; Lee, Myunghyun M; Chung, Jennifer; Al Shouli, Sadek; Fagan, Andrew; Al Khalifa, Abdulwahab; White, Christopher W; Yamashita, Michael H; Currie, Maria E; Teoh, Hwee; Mewhort, Holly E M; Verma, Subodh

    2015-12-01

    Dual antiplatelet therapy is the cornerstone treatment for patients with acute coronary syndrome. Recent Canadian Guidelines recommend the use of dual antiplatelet therapy for 1 year after coronary artery bypass grafting in patients with acute coronary syndrome, but considerable variability remains. We performed a survey of 75 Canadian cardiac surgeons to assess the use of dual antiplatelet therapy. Whereas 58.6% of respondents indicated that the benefits of dual antiplatelet therapy were seen irrespective of how patients were managed after acute coronary syndrome, 36.2% believed that the benefits of dual antiplatelet therapy were limited to those treated medically or percutaneously. In regard to the timing of dual antiplatelet therapy administration, 57% of respondents indicated that dual antiplatelet therapy should be given upstream in the emergency department, whereas 36.2% responded that dual antiplatelet therapy should be given only once the coronary anatomy has been defined. The majority surveyed (81%) weighed bleeding risk as being more important than ischemic risk reduction. In stable patients after acute coronary syndrome, the majority of surgeons would wait approximately 4 days after the last dose of P2Y12 antagonist before coronary artery bypass grafting. Only 44.6% indicated that they routinely use dual antiplatelet therapy postrevascularization in the setting of acute coronary syndrome. Rather, most surgeons use dual antiplatelet therapy for select patients, such as those with a stented vessel without a bypass graft, endarterectomy, or off-pump coronary artery bypass grafting. Cardiac surgeons exhibit variation in their attitudes and practice patterns toward dual antiplatelet therapy after coronary artery bypass grafting, and in approximately half of cases, their practice does not adhere to current guideline recommendations. New trials focusing on coronary artery bypass grafting cases in their primary analysis and educational initiatives for surgeons

  2. Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia.

    Science.gov (United States)

    Bacigalupo, Andrea; Giammarco, Sabrina; Sica, Simona

    2016-08-01

    Standard front-line treatment for acquired aplastic anemia (AA) for patients is either immunosuppressive therapy (IST) or bone marrow transplantation (BMT), usually from an HLA identical sibling. Whereas long-term survival is comparable with either treatment, important differences remain: IST patients may have incomplete or no recovery, are exposed to late clonal disorders and relapse of the original disease. Transplantation is a curative treatment, but patients are exposed to transplant-related complications both acute and chronic, such as chronic graft versus host disease (cGvHD). In the year 2000, a study by the European Group for Blood and Marrow Transplantation (EBMT), looked at failure free survival (FFS), in patients receiving first-line BMT from an HLA identical sibling, or the first-line IST. Young patients with low neutrophil counts benefited of the first-line BMT; the opposite was true for older patients with higher neutrophil counts; and a third intermediate group of patients had comparable survival irrespective of the first-line therapy. We have now studied a more recent cohort of patients to assess whether things have changed over the years. We have found similar results, although overall survival has improved, as a consequence of changes in the IST and BMT protocols.

  3. The effect of conventional immunosuppressive therapy on cytokine serum levels in pemphigus vulgaris patients.

    Science.gov (United States)

    Mortazavi, Hossein; Esmaili, Nafiseh; Khezri, Somayeh; Khamesipour, Ali; Vasheghani Farahani, Iman; Daneshpazhooh, Maryam; Rezaei, Nima

    2014-06-01

    Pemphigus vulgaris is an autoimmune disease, in which the role of Th17 cytokines needs to be further explored. This study was performed to assess serum levels of three interleukins (IL) required for Th17 differentiation (IL-1β, IL-6 and IL-23) and two specific Th17 cytokines (IL-17 and IL-22) in a group of patients with pemphigus vulgaris, at baseline, 3 weeks and 6 months after treatment. Correlations between anti-desmogleins and cytokines with disease severity as well as the influence of therapy on the above factors were assessed. Forty-three first-admitted pemphigus vulgaris patients with the active disease entered the study, but only 31 completed the study. Forty-five healthy volunteers were recruited as a control group. The patients were treated with conventional immunosuppressive therapy (oral prednisolone and azathioprine). Cytokines and anti-desmogleins were measured, using enzyme-linked immunosorbent assay. General linear model was used to evaluate the changes over time. In patients at baseline, mean serum level of IL-6 was higher, while mean levels of IL-1β and IL-22 were lower than the controls. After 3 weeks of therapy, IL-1β and IL-6 levels showed a decreasing trend, whereas IL-22 showed an increasing trend. Mean anti-desmogleins 1 and 3 values decreased significantly during the time. Anti-desmoglein values were significantly correlated with disease severity. In conclusion, IL-1β and IL-6 could be involved in the pathogenesis of pemphigus vulgaris. The positive trend of IL-22 is a new finding and should be confirmed by further studies.

  4. The efficacy of lamivudine in the treatment of reactivation of chronic hepatitis B virus infection in patients on immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Delić Dragan

    2011-01-01

    Full Text Available Introduction. Reactivation of chronic hepatitis B virus (HBV infection often occurs in hepatitis B surface antigen (HBsAg positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy. Outline of Cases. The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient’s recovery and allowed further chemotherapy. Conclusion. In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

  5. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

    2014-12-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients.

  6. The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study

    Science.gov (United States)

    D’Amico, Emanuele; Leone, Carmela; Graziano, Giusi; Amato, Maria Pia; Bergamaschi, Roberto; Cavalla, Paola; Coniglio, Gabriella; Di Battista, Giancarlo; Ferrò, Maria Teresa; Granella, Franco; Granieri, Enrico; Lugaresi, Alessandra; Lus, Giacomo; Millefiorini, Enrico; Pozzilli, Carlo; Tedeschi, Gioacchino; Zappia, Mario; Comi, Giancarlo; Trojano, Maria; Lepore, Vito; Patti, Francesco

    2016-01-01

    Introduction Immunosuppressive agents (ISA) have been used in multiple sclerosis (MS) for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS? Methods We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use. Results Out of 6,447 MS patients, 2,034 (31.6%) were treated with ISA, with Azathioprine being the most frequently used ISA overall. MS patients treated with ISA alone were more frequently affected by the progressive course (both primary and secondary) of the disease (RRR 5.82, 95% CI 4.14–8.16, p<0.0001), had higher EDSS (RRR 3.69, 95% CI 2.61–5.21, p<0.0001), higher assignment age (RRR 1.04, 95% CI 1.03–1.06, p<0.0001) than patients treated with only disease modifying drugs (DMDs). Conclusions Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population. PMID:27348606

  7. Recombinant Human Thrombopoietin Treatment Promotes Hematopoiesis Recovery in Patients with Severe Aplastic Anemia Receiving Immunosuppressive Therapy

    Directory of Open Access Journals (Sweden)

    Huaquan Wang

    2015-01-01

    Full Text Available Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO in severe aplastic anemia (SAA patients receiving immunosuppressive therapy (IST. Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000 U, subcutaneously, three times a week. rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared. Results. Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.. Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011, resp.. The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups. Conclusion. rhTPO could improve hematologic response and promote bone marrow recovery in SAA patients receiving IST.

  8. FTY720, a new immunosuppressant,as rescue therapy in mouse cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    WANGMing-Hui; VitaliyMILEKHIN; ZHANGHua; HUANGHong-Zheng

    2003-01-01

    AIM: FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induceslong-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present studyinvestigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouseheterotopic cardiac transplantation model. METHODS: BALB/c hearts were heterotopically grafted in C57BL/6mice. FTY720, at the doses of 0.5, 1, and 5 mg.kg-l.d-1 or vehicle was administered to recipients once daily by oralgavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in theperipheral blood and the peripheral lymph nodes were determined on d 5 after transplantation. RESULTS: FTY720prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed lesslymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered thenumber of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesentericlymph nodes and the peripheral lymph nodes. CONCLUSION: FTY720 used orally as rescue therapy significantlyextended allograft survival in mouse heterotopic cardiac transplantation.

  9. Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy

    Directory of Open Access Journals (Sweden)

    Foroutan N

    2013-10-01

    Full Text Available Naghmeh Foroutan,1 Hamid R Rasekh,1 Jamshid Salamzadeh,1 Hamid R Jamshidi,1 Mohsen Nafar2 1Department of Pharmacoeconomics and Pharmaceutical Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 2Department of Kidney Transplantation, Urinary Nephrology Research Center (UNRC, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Objectives: The aim of this study was to determine budget impact of conversion from cyclosporine (CsA to sirolimus (SRL in renal transplant therapy (RTT from the perspective of insurance organizations in Iran. Methods: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF, and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. Results: The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. Conclusion: To evaluate the financial consequence of adding mTOR inhibitors to the insurers’ formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with

  10. Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia.

    Science.gov (United States)

    Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Hama, Asahito; Kawashima, Nozomu; Wang, Xinan; Narita, Atsushi; Doisaki, Sayoko; Xu, Yinyan; Muramatsu, Hideki; Yoshida, Nao; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Nakamura, Kazuhiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2014-08-01

    Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (Paplastic anemia.

  11. Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.

    Science.gov (United States)

    Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

    2013-01-01

    Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.

  12. Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy

    Science.gov (United States)

    Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

    2013-01-01

    Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors. PMID:23894651

  13. Fetal fibroblasts and keratinocytes with immunosuppressive properties for allogeneic cell-based wound therapy.

    Directory of Open Access Journals (Sweden)

    Thomas Zuliani

    Full Text Available Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors.

  14. Surgical tracheotomy performed with and without dual antiplatelet therapy.

    Science.gov (United States)

    Markota, Andrej; Sinkovič, Andreja; Čizmarević, Bogdan

    2015-01-01

    Some patients who need dual antiplatelet therapy sometimes require tracheotomy. Aim of this study was to compare the rate of complications during and after surgical tracheotomy between patients requiring dual antiplatelet therapy and those without dual antiplatelet therapy. We retrospectively included 79 patients (62% men, mean age 64 ± 14 years) in the period 2007-2011. The following complications were analyzed: need for surgical revision within 24 hours after tracheotomy, need for bronchoscopy within 24 hour after tracheotomy, need for blood transfusion within 24 hours after tracheotomy, death attributed to tracheotomy and any complication attributed to tracheotomy. We compared patients where tracheotomy was performed while receiving dual antiplatelet therapy (n=27, 34%) to patients where tracheotomy was performed without dual antiplatelet therapy (n=52, 66%). Nonsignificant differences between the two groups were observed general characteristics. There were no statistically significant differences in complications after tracheotomy (surgical revision after tracheotomy p=0.63, bronchoscopy after tracheotomy p=0.74, blood transfusion after tracheotomy p=0.59, death attributed to tracheotomy p=1.00 and any complication attributed to tracheotomy p=1.00). The study shows that tracheotomy is safe in cardiac patients on dual antiplatelet therapy.

  15. Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sj(o)gren's syndrome

    Institute of Scientific and Technical Information of China (English)

    Li Hongyang; Liu Zihao; Gong Yan; Jiang Zhaocai; Zhang Yixin; Dai Yanli; Zhang Yan

    2014-01-01

    Background Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sj(o)gren's syndrome (SS).The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups:corticosteroid group (C group,methylprednisolone sodium succinate,14 patients) and corticosteroid+ immunosuppressant group (C+I group,leflunomide,13 patients).ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer (RNFL) thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher's exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive (70.4%).They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period (P <0.05); however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid.

  16. Tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis on immunosuppressive therapy.

    Science.gov (United States)

    Al-Brahim, Nabeel; Zaki, Ashraf H; El-Merhi, Khaled; Ahmad, Mahmoud S

    2013-07-01

    Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.

  17. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China

    Directory of Open Access Journals (Sweden)

    Yu Xue

    2016-01-01

    Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL and more frequently immunosuppressants than the asymptomatic group (P 1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

  18. Immunosuppressive Therapy and Bone Marrow Transplantation for Aplastic Anaemia--The CMC Experience.

    Science.gov (United States)

    George, Biju; Mathews, Vikram; Viswabandya, Auro; Abraham, Aby; Ganapule, Abhijeet; Fouzia, N A; Korula, Anu; Lakshmi, Kavitha N; Chandy, Mammen; Srivastava, Alok

    2015-03-01

    This is a single centre experience on the use of immunosuppressive therapy (IST) and stem cell transplantation (SCT) in patients with aplastic anaemia. Between 1985 and December 2013, 530 patients underwent IST while 214 underwent allogeneic SCT. Overall response rate with the use of IST was 58% with higher responses seen in adults (65.1%) compared to children (35.8%) [p = 0.001]. At a median follow up of 34 months (range: 1 - 264), 5 year KM estimates for OS for the entire group is 68.2 ± 2.2%. Loss of response or relapse was seen in 27 responders while clonal evolution to PNH was seen in 8 patients and transformation to MDS or AML was seen in 3. The 5 yr OS for children (45.7 ± 4.7%) was significantly lower than the OS of age groups 16-30 (75.6 ± 3.6%), 31-50 years (76.2 ± 4.2%) and > 50 years (73.0 ±4.2%) (p = 0.0001). SCT was performed in 214 patients with engraftment seen in 91%. The incidence of grade II-IV acute graft versus host disease (GVHD) was 38.4% with grade III-IV GVHD in 11.7%. Chronic GVHD was seen in 47.5% of evaluable patients with majority (73%) being limited chronic GVHD. At a median follow up of 32 months (range: 1 - 244), the 5 year KM estimates of OS for the entire cohort is 64.8 ± 3.3%); The 5 yr OS was significantly higher with the use of Flu/Cy (5 yr OS of 73.8 ± 3.6%) compared to Cy/ATG (5 yr OS of 44.4 ± 9.6%) or Flu/Bu conditioning (5 yr OS of 52.4 ± 8.9%) [p = 0.001]. Imp: SCT and IST offer good response rates and survival in Indian patients with AA except in children receiving IST.

  19. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    Science.gov (United States)

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-08-01

    End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations

  20. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    Science.gov (United States)

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-01-01

    BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI

  1. [Effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy and research the drug resistance].

    Science.gov (United States)

    Lu, Li-Xia; Wang, Ying; Lu, Xiao-Jun; Li, Da-Jiang; Xu, Kong-Wen; Tang, Hong; Liu, Li; Liu, Cong; Wang, Li-Chun

    2011-09-01

    To study the effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy, and research the drug resistance. Thirty-one cases of chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents therapy were enrolled and divided into two group, HBeAg-positive group (n = 20) and HBeAg-negative group (n = 11), then given Lamivudine for preventive treatment. Virus response, biochemical response and serum response were evaluated as effective index, and analyzed the difference between the two groups for statistical significance. Meanwhile, drug resistance rate, impact factor of resistance and security were analyzed. At the end of 48 weeks' treatment, the rate of HBV DNA under the detection limit was 41.94%, and the decline of HBV DNA compared with baseline was 2.35 lg. The normalization rate of ALT, the negative rate of HbeAg and the seroconversion rate of HBeAg/HBeAb were 92.31%, 25% and 20% respectively. HBeAg-positive group and HBeAg-negative group patients in the complete virus response, the decline of HBV DNA compared with baseline and the resistance rate had no statistics significance (P > 0.05). At the same time, virology breakthrough occurred in four patients, and resistance mutation was detected in three cases among them. The resistance rate was 9.68%. The type of genotype mutation were all rtM204I. Multi-factor regression analysis showed that the baseline factors including age, gender, HBeAg status, baseline HBV DNA level and baseline ALT had no significant compact on drug resistance. Serious adverse reactions were not found in all patients. For chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents treatment, Lamivudine for preventive antiviral therapy is a good option with good antiviral effect and safety. It is necessary to pay attention to the occurrence of drug resistance.

  2. [Clinical impact of dual antiplatelet therapy on peptic ulcer disease].

    Science.gov (United States)

    Ahn, Dae Geon; Kim, Beom Jin; Kim, Jeong Wook; Kim, Jae Gyu

    2014-08-01

    Increased incidence of coronary artery disease has led to the increased use of dual antiplatelet therapy composed of aspirin and clopidogrel. We investigated the incidence of gastrointestinal complications in patients who received single or dual antiplatelet therapy and analyzed their clinical characteristics in order to predict the prognostic factors. Between January 2009 and December 2011, we retrospectively reviewed the medical records of patients who underwent coronary angiography at Chung-Ang University Hospital (Seoul, Korea). One hundred and ninety-four patients were classified into two groups: aspirin alone group and dual antiplatelet group. Clinical characteristics, past medical history, and presence of peptic ulcer were analyzed. During the follow-up period, 11 patients had duodenal ulcer; the event rate was 2.02% in the aspirin alone group and 9.47% in the dual antiplatelet group (hazard ratio [HR] 5.24, 95% CI 1.03-26.55, pantiplatelet groups had a higher incidence of duodenal ulcers without significant bleeding compared with the aspirin alone group. In patients who received PPI, the dual antiplatelet therapy group had a higher incidence of gastric ulcers without significant bleeding compared with the aspirin alone group. Therefore, physicians must pay attention to high risk groups who receive dual antiplatelet therapy and aggressive diagnostic endoscopy should also be considered.

  3. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    María Luisa Manzano-Alonso; Gregorio Castellano-Tortajada

    2011-01-01

    Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus (HBV) replication,often accompanied by an increase in serum transaminase levels, and both events occurring in a patient with a previous inactive hepatitis B infection. This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered. It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases. Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis, which are sometimes serious and result in acute liver failure with risk of death, and usually occur in the periods between cycles or at the end of chemotherapy. Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen (HBsAg) or anti-HBc, but much less frequently than chemotherapy treatments. The tumor necrosis factor α inhibitors infliximab, etanercept and adalimumab may cause reactivation of hepatitis B, and the overall frequency with infliximab may be similar (50%-66%) to that caused by chemotherapy. Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs, and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.

  4. Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation.

    Science.gov (United States)

    Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Crathorne, Louise; Cooper, Chris; Varley-Campbell, Jo; Mujica-Mota, Ruben; Coelho, Helen; Huxley, Nicola; Lowe, Jenny; Dudley, Jan; Marks, Stephen; Hyde, Chris; Bond, Mary; Anderson, Rob

    2016-08-01

    End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS

  5. Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation.

    Science.gov (United States)

    Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Crathorne, Louise; Cooper, Chris; Varley-Campbell, Jo; Mujica-Mota, Ruben; Coelho, Helen; Huxley, Nicola; Lowe, Jenny; Dudley, Jan; Marks, Stephen; Hyde, Chris; Bond, Mary; Anderson, Rob

    2016-01-01

    BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. DATA SOURCES Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE

  6. Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cristina Costa

    2012-03-01

    Full Text Available Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN, possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens: in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0% and 12 (2.0% specimens from 40 (11.0% and 11 (10.4% patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2% and 58 (9.8% specimens from 67 (18.5% and 27 (25.5% patients, being the difference of incidence highly significant (p <0.0001 for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation.

  7. Post-transplant aspergillosis and the role of combined neurosurgical and antifungal therapies under belatacept immunosuppression

    DEFF Research Database (Denmark)

    Ekkehard, Kasper; Bartek, Jiri; Johnson, Jesper Scott

    2011-01-01

    into our institution in June 2007 with speech difficulties and gait instability 1.5 years after cadaveric kidney transplantation. On imaging, both a mediastinal and left frontal mass were found. Radiographically guided sampling of the mediastinal mass and a stereotactic biopsy of the left frontal brain......Opportunistic CNS-infection represent a major threat to patients after organ transplantation due to the need for ongoing immunosuppression and belatacept is a novel CTL4A inhibitor, which is increasingly used for patients following cadaveric kidney transplantation. Among the CNS infections...

  8. From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Raghavan Chinnadurai

    2013-01-01

    Full Text Available The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS, linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.

  9. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naive recipients.

    Science.gov (United States)

    Yusuf, Nabiha; Katiyar, Santosh K; Elmets, Craig A

    2008-01-01

    Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4+ and CD8+ T cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, nontumor-bearing CD4 knockout (CD4-/-) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg kg(-1) Pc4, 110 J cm(-2) light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4-/- mice compared with WT mice. We next examined the role of CD8+ T cells in Pc4-PDT-induced immunosuppression using CD8-/- mice following the same treatment regimen used for CD4-/- mice. Similar to CD4-/- mice, CD8-/- mice exhibited less immunosuppression than WT mice. Pc4-PDT-induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (P PDT-induced immunosuppression but do not affect PDT-induced regression of tumors may prove superior to PDT alone in promoting long-term antitumor responses.

  10. Dual RAS Therapy Not on Target, but Fully Alive

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; de Zeeuw, D.

    2010-01-01

    Inhibitors of the renin-angiotensin system (RAS) form a cornerstone in the treatment of kidney disease. These drugs lower blood pressure and albuminuria, and afford renal protection. Dual therapy with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker have been shown to be m

  11. Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: Report of two cases

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    Reddy I

    2005-01-01

    Full Text Available Disseminated strongyloidiasis is a rare manifestation in patients on immunosuppressive drugs. We report two cases of fatal disseminated Strongyloides stercoralis infestation. The first was in a patient of pemphigus vulgaris who developed an exacerbation of symptoms, one year after diagnosis and was given intravenous dexamethasone and azathioprine and in the third week of hospitalization developed features of septicemia, respiratory failure and petechial hemorrhages which were proven to be due to disseminated strongyloidiasis. The second patient was diagnosed to have stage IV diffuse large cell type of non-Hodgkin lymphoma and after the second cycle of chemotherapy, developed generalized symptoms of septicemia, respiratory failure, purpuric macules and patches. This was also proven to be disseminated strongyloidiasis.

  12. Association of Anti-PLA2R Antibodies with Outcomes after Immunosuppressive Therapy in Idiopathic Membranous Nephropathy

    Science.gov (United States)

    Hofstra, Julia M.; Brenchley, Paul E.; Wetzels, Jack F.M.

    2014-01-01

    Background The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate. Design, setting, participants, & measurements This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA. Results In total, 48 patients (37 men) were included. The median age was 55 years (range, 34–75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98–3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab–positive patients, treatment resulted in a rapid decrease of antibodies: median anti–PLA2R-ab, 428 U/ml (range, 41–16,260 U/ml) at baseline and 24 U/ml (range, 0–505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003). Conclusions These data suggest that in PLA2R-ab–positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course. PMID:25035272

  13. Music Therapy Interventions for Deaf Clients with Dual Diagnosis

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    Anna Johnson Ward

    2016-11-01

    Full Text Available The current music therapy literature addresses the use of music with the Deaf population, particularly those with cochlear implants. However, few studies or descriptions of music therapy with Deaf individuals who are dually diagnosed with an emotional or behavioral disorder and an intellectual disability have been conducted. Given that music therapy has been found to be an effective intervention for both Deaf individuals and individuals with emotional or behavioral needs, ideas and resources for music therapists working with this population are needed. These case examples provide a description of music therapy for individuals who were dually diagnosed in a residential mental health facility. Music therapy experiences and their effectiveness for Deaf patients with dual diagnoses are presented as well as cultural aspects of music within the Deaf community and their implications for creating music therapy interventions.

  14. Impact of everolimus: update on immunosuppressive therapy strategies and patient outcomes after renal transplantation

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    Helio Tedesco-Silva Jr

    2011-01-01

    Full Text Available Helio Tedesco-Silva Jr, Claudia Rosso Felipe, Tainá Veras de Sandes Freitas, Marina Pontello Cristeli, Carolina Araújo Rodrigues, José Osmar Medina PestanaNephrology Division, Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, BrazilAbstract: Everolimus is an immunosuppressive agent used for the prophylaxis of acute rejection after kidney transplantation. Everolimus inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR, a key enzyme that controls cell growth and metabolism, producing cell cycle arrest from the G1 to S phase. As a consequence, everolimus has antiproliferative and antineoplastic effects. Everolimus is a drug with a narrow therapeutic index. The pharmacokinetics of everolimus indicates a need for twice-daily dosing. Intra- and interindividual variability and drug–drug interactions suggest the need for therapeutic drug monitoring to maximize the efficacy/toxicity ratio. The good correlation between exposure (area under the concentration–time curve and trough concentration indicates that monitoring of everolimus trough concentrations is an adequate strategy after kidney transplantation. Everolimus is indicated for low- to moderate-risk de novo kidney transplant candidates. There are no conclusive studies thus far indicating that everolimus can be used in high-risk patients, such as sensitized patients, retransplants, and African Americans. In de novo kidney transplant recipients, the recommended initial dose of everolimus is 0.75 mg twice daily, adjusted to maintain blood trough concentrations of 3–8 ng/mL, in combination with progressive reduction in blood trough cyclosporine concentrations to 25–50 ng/mL. In combination with reduced trough blood tacrolimus concentrations of 4–7 ng/mL the recommended initial dose of everolimus is 1.5 mg twice daily, adjusted to maintain trough blood concentrations of 3–8 ng/mL. Everolimus can also be used as a conversion strategy

  15. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; model was used to identify factors associated with nonadherence. In total, 808/946 recipients (85.4%) provided ≥1 ITAS score. Nonadherence was reported by 24.8%, 31.5%, 33.0%, 39.8%, 35.4% and 26.4% at months 3, 6, 12, 24, 36 and 48, respectively. Mean ITAS score was higher with EC-MPS vs. MMF at months 24 (11.3[1.0] vs. 10.9[1.4], p=0.001) and 36 (11.4[1.0] vs. 11.1[11.3], p=0.024). The odds ratio for nonadherence was 1.60 (95% CI 1.17, 2.19; p=0.003) for African Americans vs. non-African Americans. The rate of biopsy-proven acute rejection was 12.7% (51/401) in nonadherent recipients vs. 11.3% (46/406) in adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  16. Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

    Science.gov (United States)

    Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco

    2015-01-01

    Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. PMID:26307985

  17. Impact of Single Nucleotide Polymorphisms (SNPs on Immunosuppressive Therapy in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Jesus Ruiz

    2015-08-01

    Full Text Available Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA, during the first six months after lung transplantation (51 patients. The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc. The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC. In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%. Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.

  18. Reduced raltegravir clearance in HIV-infected liver transplant recipients: an unexpected interaction with immunosuppressive therapy?

    Science.gov (United States)

    Cattaneo, Dario; Puoti, Massimo; Sollima, Salvatore; Moioli, Cristina; Foppa, Caterina Uberti; Baldelli, Sara; Clementi, Emilio; Gervasoni, Cristina

    2016-05-01

    Liver transplantation (LTx) is considered a safe procedure in selected HIV-infected patients. In this clinical setting raltegravir is the antiretroviral of choice due to its optimal tolerability and its negligible interactions with immunosuppressive drugs. We aimed at providing data on the pharmacokinetics of raltegravir in LTx recipients, on which the available information is inconclusive. In this retrospective multicentre study we characterized the pharmacokinetics of raltegravir in a consecutive series of HIV-infected LTx recipients referred to our laboratory for therapeutic drug monitoring (TDM) and compared the obtained profiles with those collected from a control group of HIV-infected patients. Seventeen HIV-infected LTx patients were considered. LTx recipients had significantly higher raltegravir AUC0-12 compared with the control group of HIV-infected patients [14 314 (11 627-19 998) versus 8795 (5218-12 954) ng·h/mL; P < 0.01]. Two LTx patients experienced moderate increments in serum transaminases, nausea and vomiting that improved after raltegravir dose reduction. High raltegravir exposure and acceptable safety profile were observed in HIV-infected LTx recipients. Our results highlight that some patients may obtain an advantage from TDM-guided raltegravir dose adjustments with potential benefits in terms of drug tolerability. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Long-term immunosuppressive therapy with cyclosporine plus prednisolone for necrotizing meningoencephalitis in a Pekingese dog.

    Science.gov (United States)

    Jung, Dong-In; Kim, Ju-Won; Park, Hee-Myung

    2012-06-01

    A 4-year-old intact female Pekingese dog was presented with ataxia and seizure episodes. Based on magnetic resonance imaging and cerebrospinal fluid analysis results, meningoencephalitis of unknown etiology was suspected. The present case survived for 1,096 days under cyclosporine plus prednisolone therapy and was definitively diagnosed with necrotizing meningoencephalitis. This report describes the clinical findings, serial magnetic resonance imaging characteristics and pathologic features of a necrotizing meningoencephalitis and long-term survival after cyclosporine with prednisolone therapy.

  20. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    Science.gov (United States)

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia.

  1. Duration of dual antiplatelet therapy in acute coronary syndrome

    Science.gov (United States)

    Wilson, Simon John; Newby, David E; Dawson, Dana; Irving, John; Berry, Colin

    2017-01-01

    Despite a large volume of evidence supporting the use of dual antiplatelet therapy in patients with acute coronary syndrome, there remains major uncertainty regarding the optimal duration of therapy. Clinical trials have varied markedly in the duration of therapy, both across and within trials. Recent systematic reviews and meta-analyses suggest that shorter durations of dual antiplatelet therapy are superior because the avoidance of atherothrombotic events is counterbalanced by the greater risks of excess major bleeding with apparent increases in all-cause mortality with longer durations. These findings did not show significant heterogeneity according to whether patients had stable or unstable coronary heart disease. Moreover, the potential hazards and benefits may differ when applied to the general broad population of patients encountered in everyday clinical practice who have markedly higher bleeding and atherothrombotic event rates. Clinicians lack definitive information regarding the duration of therapy in patients with acute coronary syndrome and risk scores do not appear to be sufficiently robust to address these concerns. We believe that there is a pressing need to undertake a broad inclusive safety trial of shorter durations of therapy in real world populations of patients with acute coronary syndrome. The clinical evidence would further inform future research into strategies for personalised medicine. PMID:28249994

  2. Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease

    Directory of Open Access Journals (Sweden)

    Ihrler Stephan

    2009-05-01

    Full Text Available Abstract Background Herpes simplex virus type-1 (HSV-1 has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. Methods We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. Results 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. Conclusion The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study

  3. Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis,with a special focus on corticosteroid therapy

    Institute of Scientific and Technical Information of China (English)

    Pilar López-Serrano; Elsa de la Fuente Briongos; Elisa Carrera Alonso; Jose Lázaro Pérez-Calle; Conrado Fernández Rodríguez

    2015-01-01

    Currently immunosuppressive and biological agentsare used in a more extensive and earlier way inpatients with inflammatory bowel disease, rheumaticor dermatologic diseases. Although these drugs haveshown a significant clinical benefit, the safety of thesetreatments is a challenge. Hepatitis B virus (HBV)reactivations have been reported widely, even includingliver failure and death, and it represents a deep concernin these patients. Current guidelines recommend to preemptivetherapy in patients with immunosuppressantsin general, but preventive measures focused in patientswith corticosteroids and inflammatory diseases arescarce. Screening for HBV infection should be done atdiagnosis. The patients who test positive for hepatitisB surface antigen, but do not meet criteria for antiviraltreatment must receive prophylaxis before undergoingimmunosuppression, including corticosteroids at higherdoses than prednisone 20 mg/d during more than twoweeks. Tenofovir and entecavir are preferred thanlamivudine because of their better resistance profile inlong-term immunosuppressant treatments. There is nota strong evidence, to make a general recommendationon the necessity of prophylaxis therapy in patientswith inflammatory diseases that are taking low dosesof corticosteroids in short term basis or low systemicbioavailability corticosteroids such as budesonide orbeclomethasone dipropionate. In these cases regularlyHBV DNA monitoring is recommended, starting earlyantiviral therapy if DNA levels begin to rise. In patientswith occult or resolved hepatitis the risk of reactivationis much lower, and excepting for Rituximab treatment,the prophylaxis is not necessary.

  4. [Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy].

    Science.gov (United States)

    Kuramitsu, Shotaro; Iguchi, Tomohiro; Ninomiya, Mizuki; Yamashita, Yo-ichi; Harimoto, Norifumi; Ikegami, Toru; Uchiyama, Hideaki; Yoshizumi, Tomoharu; Soejima, Yuji; Shirabe, Ken; Kawanaka, Hirofumi; Ikeda, Tetsuo; Furuta, Toshiya; Tamada, Ryuichiro; Maehara, Yoshihiko

    2014-03-01

    Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction.

  5. From immunosuppression to tolerance.

    Science.gov (United States)

    Adams, David H; Sanchez-Fueyo, Alberto; Samuel, Didier

    2015-04-01

    The past three decades have seen liver transplantation becoming a major therapeutic approach in the management of end-stage liver diseases. This is due to the dramatic improvement in survival after liver transplantation as a consequence of the improvement of surgical and anaesthetic techniques, of post-transplant medico-surgical management and of prevention of disease recurrence and other post-transplant complications. Improved use of post-transplant immunosuppression to prevent acute and chronic rejection is a major factor in these improved results. The liver has been shown to be more tolerogenic than other organs, and matching of donor and recipients is mainly limited to ABO blood group compatibility. However, long-term immunosuppression is required to avoid severe acute and chronic rejection and graft loss. With the current immunosuppression protocols, the risk of acute rejection requiring additional therapy is 10-40% and the risk of chronic rejection is below 5%. However, the development of histological lesions in the graft in long-term survivors suggest atypical forms of graft rejection may develop as a consequence of under-immunosuppression. The backbone of immunosuppression remains calcineurin inhibitors (CNI) mostly in association with steroids in the short-term and mycophenolate mofetil or mTOR inhibitors (everolimus). The occurrence of post-transplant complications related to the immunosuppressive therapy has led to the development of new protocols aimed at protecting renal function and preventing the development of de novo cancer and of dysmetabolic syndrome. However, there is no new class of immunosuppressive drugs in the pipeline able to replace current protocols in the near future. The aim of a full immune tolerance of the graft is rarely achieved since only 20% of selected patients can be weaned successfully off immunosuppression. In the future, immunosuppression will probably be more case oriented aiming to protect the graft from rejection and at

  6. Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Keiichi Fujiwara; Osamu Yokosuka; Hiroshige Kojima; Tatsuo Kanda; Hiromitsu Saisho; Hiroyuki Hirasawa; Hiroshi Suzuki

    2005-01-01

    AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose"group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose"group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose"group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically lifethreatening" severe exacerbation of chronic hepatitis B,when used in the early stage of illness.

  7. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results.

    Science.gov (United States)

    Bowen, J D; Kraft, G H; Wundes, A; Guan, Q; Maravilla, K R; Gooley, T A; McSweeney, P A; Pavletic, S Z; Openshaw, H; Storb, R; Wener, M; McLaughlin, B A; Henstorf, G R; Nash, R A

    2012-07-01

    The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ≥1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of ≤6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.

  8. Teratogenesis and immunosuppressive treatment.

    Science.gov (United States)

    Danesi, R; Del Tacca, M

    2004-04-01

    Despite the potential risks to the mother and fetus caused by immunosuppressive drugs, uneventful pregnancies are now frequent among transplant recipients. Although there is no apparent increase in the type or incidence of malformations in the newborns or evidence of graft dysfunction, pregnancy-related complications, including premature termination and low birth weight, may be more frequent. To prevent graft rejection due to the increased immunologic reactivity of the transplant recipient during pregnancy, it is reasonable to wait 2 years after transplantation before conception, to have stable graft function and to be on low drug doses for maintenance immunosuppression. Among the immunosuppressive agents, corticosteroids may induce a number of treatment-related complications, including diabetes and osteoporosis; however, the incidence of fetal malformations during corticosteroid treatment is about 3.5%, a value close to that of the general population. Among immunosuppressive antibodies, no evidence of developmental toxicity has been demonstrated with basiliximab. On the contrary, some concerns have been raised about azathioprine, since its use has been associated with fetal abnormalities in animals; however, clinical data so far have indicated only a small teratogenic risk. Therefore, immunosuppressive therapy with selected drugs and antibodies does not apparently increase the risk of birth defects and may be continued in pregnancy. Finally, although breast-feeding is not recommended, because of drug transfer into maternal milk, the available clinical data do not support this limitation because of the low amount of drug absorbed by the infant and the absence of clinical toxicity in published case reports.

  9. Clinical Lessons to Be Learned from Patients Developing Chronic Myeloid Leukemia While on Immunosuppressive Therapy after Solid Organ Transplantation: Yet Another Case after Orthotopic Heart Transplantation

    Directory of Open Access Journals (Sweden)

    Christian Oberender

    2014-01-01

    Full Text Available Chronic myeloid leukemia developing after transplantation of solid organs and concomitant immunosuppression is a rare but still significant clinical phenomenon. We here describe an additional case of a 62-year-old male patient developing CML after orthotopic heart transplantation and medication with cyclosporine A, mofetil-mycophenolate, and steroids. Initial antileukemic therapy was imatinib at a standard dose and within 15 months of therapy a complete cytogenetic response was noted. In this report we discuss the clinical implications of these rare but biologically important cases.

  10. Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study.

    Science.gov (United States)

    Resor, Charles D; Nathan, Ashwin; Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Cutlip, Donald E; Gabriel Steg, P; Hsieh, Wen-Hua; Mauri, Laura

    2016-10-04

    Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events. Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P=0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29-0.58; Ptherapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding. URL: http://clinicaltrials.gov. Unique identifier: NCT00977938. © 2016 American Heart Association, Inc.

  11. Immunosuppressive strategies and management

    Institute of Scientific and Technical Information of China (English)

    Shi-hui PAN

    2008-01-01

    Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival.However,chronic allograft failure,antibody mediated rejection,recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life.New immunosuppressive agents and protocols are being evaluated to combat these problems.Importantly,clinicians must work to manage post-transplant complications and avoid complex medication regimens,which will potentiate drug interactions and non.compliance.Different organs have different immunogenicities and each recipient has a unique clinical and immunologic profile.The clinician must recognize these variations and customize the immunosuppressive regimens and treatment protocols based on the individual condition.The general principles of an individualized immunosuppressive protocol should take the following factors into account:organ type,donor and recipient characteristics,quality of the donor organ,recipienVs medical history,recipient's undedying disease,immunologic risk for acute rejection,potential co-morbidity related to immunosuppression,significant druginteractions,medication costs and patient compliance.In addition,the combination of immunosuppressive drugs must have a pharmacologic rationale to achieve the desired goal of suppressing the individual's immune system to render the patient tolerant to the allograft while minimizing co-morbidities.For the past few years,many clinical strategies have been applied in an attempt to improve graft survival or to reduce immunsuppressants induced side-effects.Specific protocols include steroid or CNI avoidance,minimization or withdraw,desensitization,and treatment for antibody mediated rejection,disease specific,and pediatric specific.The short-term outcomes from these different strategies are promising but the long-term results remain to be determined.Unfortunately,current immunosuppressive agents or strategies

  12. New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.

    Science.gov (United States)

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe

    2016-12-15

    The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.

  13. Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection.

    Science.gov (United States)

    Tang, L; Ward, H; Kattakuzhy, S; Wilson, E; Kottilil, S

    2016-01-01

    Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

  14. DUAL ANTIPLATELET THERAPY IN THE REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. N. Guseva

    2015-09-01

    Full Text Available Aim. To evaluate an adequacy of dual antiplatelet therapy (DAPT in patients with acute coronary syndrome (ACS with ST segment elevation and bare metal stent implantation after hospital discharge.Material and methods. 311 patients with ACS with ST segment elevation were included into the study. All of them underwent percutaneous coronary intervention with bare metal stent implantation. The information was obtained by the telephone survey.Results. 54.5% of patients received DAPT during 12 months. 43.8% of patients also received combination of clopidogrel and acetylsalicylic acid, but changed medicinal products of clopidogrel due to different reasons. 1.7% of patients received acetylsalicylic acid only.Conclusion. More than 50% of patients received recommended DAPT at that they preferred generic drugs of clopidogrel original one.

  15. Dual antiplatelet therapy after noncardioembolic ischemic stroke or transient ischemic attack: pros and cons.

    Science.gov (United States)

    Hong, Keun-Sik

    2014-07-01

    Dual antiplatelet therapy simultaneously blocks different platelet activation pathways and might thus be more potent at inhibiting platelet activation and more effective at reducing major ischemic vascular events compared to antiplatelet monotherapy. Aspirin plus clopidogrel dual therapy is now the standard therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. However, dual antiplatelet therapy carries an increased risk of bleeding. Patients with ischemic stroke or transient ischemic attack (TIA) are generally older and likely to have a fragile cerebrovascular bed, which further increases the risk of systemic major bleeding events and intracranial hemorrhage. Clinical trials and meta-analyses suggest that in comparison to antiplatelet monotherapy, dual antiplatelet therapy initiated early after noncardioembolic ischemic stroke or TIA further reduces the rate of recurrent stroke and major vascular events without significantly increasing the rate of major bleeding events. In contrast, studies of long-term therapy in patients with noncardioembolic ischemic stroke or TIA have yielded inconsistent data regarding the benefit of dual antiplatelet therapy over monotherapy. However, the harm associated with major bleeding events, including intracranial hemorrhage, which is generally more disabling and more fatal than ischemic stroke, is likely to increase with dual antiplatelet therapy. Physicians should carefully assess the benefits and risks of dual antiplatelet therapy versus antiplatelet monotherapy when managing patients with ischemic stroke or TIA.

  16. Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity.

    NARCIS (Netherlands)

    Buf-Vereijken, P.W.G. du; Wetzels, J.F.M.

    2004-01-01

    BACKGROUND: A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of

  17. Efficacy and safety of single versus dual antiplatelet therapy for coiling of unruptured aneurysms.

    Science.gov (United States)

    Nishikawa, Yusuke; Satow, Tetsu; Takagi, Toshinori; Murao, Kenichi; Miyamoto, Susumu; Iihara, Koji

    2013-07-01

    Although the efficacy of antiplatelet therapy for coiling of unruptured cerebral aneurysms has been reported, regimens for this therapy are not yet well established. The aim of this retrospective study was to analyze correlations among the modes of antiplatelet use, aneurysmal configuration, coiling methods, and complications to elucidate the optimal antiplatelet therapy for coiling. The study population comprised 154 patients with unruptured aneurysms who underwent coiling with antiplatelet therapy at our institution between 2001 and 2009. The patients were categorized by mode of antiplatelet therapy (single [n = 64] or dual [n = 90]), neck size (wide [n = 80] or narrow [n = 74]), and technique used (simple [n = 42] or adjunctive [n = 112]). The incidences of hemorrhagic/ischemic complications and abnormalities on postprocedural diffusion-weighted magnetic resonance imaging (DWI) in each group were statistically assessed. Hemorrhagic complications occurred in 1 case (1.5%) with single antiplatelet therapy and in 2 cases (2.2%) with dual antiplatelet therapy. Symptomatic ischemic complications occurred in 5 cases (7.8%) with single therapy and in 4 cases (4.4%) with dual therapy. Abnormalities were detected by DWI in 27 cases (42%) with single therapy and in 31 cases (34%) with dual therapy. No significant difference was found between modes of antiplatelet therapy even when the technique used was taken into account. In cases of wide neck, however, there were significant differences in the rate of symptomatic ischemic complications (single, 21.7%; dual, 3.5%; P = .014) and DWI abnormalities (single, 37.8%; dual, 20.9%; P = .048). Our data suggest that dual antiplatelet therapy may better prevent ischemic complications from coiling for wide-necked aneurysms compared with single antiplatelet therapy. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. The underutilisation of dual antiplatelet therapy in acute coronary syndrome.

    Science.gov (United States)

    Anastasius, Malcolm; Lau, Jerrett K; Hyun, Karice; D'Souza, Mario; Patel, Anushka; Rankin, Jamie; Walters, Darren; Juergens, Craig; Aliprandi-Costa, Bernadette; Yan, Andrew T; Goodman, Shaun G; Chew, Derek; Brieger, David

    2017-08-01

    Despite guideline recommendation of dual antiplatelet therapy (DAPT) in treating ACS, DAPT is underutilized. Our objective was to determine independent predictors of DAPT non-prescription in ACS and describe pattern of DAPT prescription over time. Patients presenting to 41 Australian hospitals with an ACS diagnosis between 2009 and 2016 were stratified according to discharge prescription with DAPT and single antiplatelet therapy (SAPT) or no antiplatelet therapy. Multiple stepwise logistic regression, accounting for within hospital clustering, was used to determine the independent predictors of DAPT non-prescription, defined as discharge with SAPT alone or no antiplatelet agent. 8939 patients survived to discharge with an ACS diagnosis. Of these, 6294 (70.4%) patients were discharged on DAPT, 2154 (24.1%) on SAPT and 491 (5.5%) on no antiplatelet agent. Independent predictors of DAPT non-prescription in the overall cohort were: in-hospital CABG (OR 0.09, 95%CI 0.05-0.14), discharge with warfarin (0.10 (0.07-0.14)), in hospital major bleeding (0.48 (0.34-0.67), diagnosis of unstable angina (0.35, (0.27-0.45)), non-ST-elevation myocardial infarction (0.67 (0.57-0.78)) [both vs. ST-segment elevation myocardial infarction], in hospital atrial arrhythmia (0.72 (0.60-0.86)), history of hypertension (0.83 (0.73-0.94)) and GRACE high risk (0.83 (0.71-0.98)). There was an increase in prescription of DAPT and a shift towards ticagrelor over clopidogrel for ACS from 2013 to 2016 (pantiplatelet management. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy (DAPT) Study

    Science.gov (United States)

    Resor, Charles D; Nathan, Ashwin; Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Cutlip, Donald E; Steg, P. Gabriel; Hsieh, Wen-Hua; Mauri, Laura

    2017-01-01

    Background Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. Methods The Dual Antiplatelet Therapy Study, a double-blind trial, randomized 11,648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, beta blocker and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use in patients with an ACC/AHA class I indication for each medication. Per protocol, all patients were treated with aspirin 75–325 mg daily. Endpoints included myocardial infarction (MI), major adverse cardiovascular and cerebrovascular events (MACCE) and GUSTO moderate or severe bleeding events. Results Of 11,643 randomized patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced MI compared with placebo in both groups (on OMT 2.1% vs 3.3%, HR 0.64, CI 0.48–0.86, p=0.003; off OMT 2.2% vs 5.2%, HR 0.41, CI 0.29–0.58, p OMT (HR 0.82, CI 0.66–1.02, p=0.077) and 4.5% vs 7.0% among those off OMT (HR 0.63, CI 0.49–0.82, pOMT were 2.2% vs 1.0% (HR 2.13, CI 1.43–3.17, pOMT were 2.8% vs 2.2% (HR 1.30, CI 0.88–1.92, p=0.189; interaction p=0.073). Overall, patients on OMT had lower rates of MI (2.7% vs 3.7%, p=0.003), MACCE (4.6% vs 5.7%, p=0.007) and bleeding (1.6% vs 2.5%, pOMT. Rates of stent thrombosis (0.8% vs 1.0%, p=0.171) and death (1.6% vs 1.9%, p=0.155) did not differ. Conclusions Continued thienopyridine therapy reduced the rate of MI regardless of OMT status and had consistent effects on reduction in MACCE and increased bleeding. Trial Registration https://clinicaltrials.gov, #NCT00977938 PMID:27576774

  20. [Clinical observation of treating 62 patients with severe aplastic anemia failing in immunosuppressive therapy by integrative medicine].

    Science.gov (United States)

    Su, Er-yun; Fang, Yu-hua; Chen, Hui-shu

    2012-12-01

    To explore treatment methods for patients with severe aplastic anemia (SAA) failing in immunosuppressive therapy (IST). Totally 62 SAA patients failing in IST were treated by integrative medicine (IM). The treatment course was divided into three stages: the critical emergency stage, the improvement stage, and the recovery stage. In the critical emergency stage, patients were treated with Lingyang Yigui Decoction (LYD, consisting of 1.2 g antelope horn, 6 g coptis chinensis, 12 g stir-baked Fructus Gardeniae, 30 g rehmannia rhizoma, 50 g lalang grass rhizome, 9 g amur corktree bark, 12 g Cortex Moutan, 9 g ass-hide gelatin, 30 g red date, 6 g prepared licorice root, etc.) and Erzhi Busui Decoction (EBD, consisting of 120 g glossy privet fruit, 100 g eclipta prostrata, 24 g prepared Gold Theragran, 12 g fructus lycii, 90 g rehmannia rhizoma, 60 g astragalus, 9 g Angelica sinensis, 9 g ass-hide gelatin, 30 g honeysuckle flower, 12 g lotus plumule, and so on) alternatively, one dose daily, decocted twice, taken in two portions. Meanwhile, 50 mg Testosterone Propionate was intramuscularly injected every other day to the improvement stage. Those with fever were treated with LYD by adding 60 g gypsum, 60 g common anemarrhena, 30 g dandelion, 30 g bittersweet herb, 30 g blackend swallowwort root and rhizome, 15 g hemsley rockvine root tuber, and so on. In the improvement stage patients were treated with Jixueteng Compound (Jixueteng Zhengyang Decoction was administered to those of Shen-yang deficiency syndrome: consisting of 100 g spatholobus suberectus, 60 g astragalus, 3 g red ginseng, 12 g psoralea corylifolia, 18 g dodder seed, 12 g angelica, 18 g Herba Epimedii, 6 g common fenugreek seed, 24 g Gold Theragran, 30 g glossy privet fruit, 30 g eclipta prostrata, 6 g dried human placenta, and so on). Meanwhile, 50 mg Testosterone Propionate was intramuscularly injected every other day. Jixueteng Yijing Decoction was administered to those of Shen-yin deficiency syndrome

  1. Immunosuppressive mechanisms in glioblastoma.

    Science.gov (United States)

    Nduom, Edjah K; Weller, Michael; Heimberger, Amy B

    2015-11-01

    Despite maximal surgical and medical therapy, the treatment of glioblastoma remains a seriously vexing problem, with median survival well under 2 years and few long-term survivors. Targeted therapy has yet to produce significant advances in treatment of these lesions in spite of advanced molecular characterization of glioblastoma and glioblastoma cancer stem cells. Recently, immunotherapy has emerged as a promising mode for some of the hardest to treat tumors, including metastatic melanoma. Although immunotherapy has been evaluated in glioblastoma in the past with limited success, better understanding of the failures of these therapies could lead to more successful treatments in the future. Furthermore, there is a persistent challenge for the use of immune therapy to treat glioblastoma secondary to the existence of redundant mechanisms of tumor-mediated immune suppression. Here we will address these mechanisms of immunosuppression in glioblastoma and therapeutic approaches.

  2. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients.

    Science.gov (United States)

    Muduma, Gorden; Shupo, Francis C; Dam, Sophie; Hawken, Natalia A; Aballéa, Samuel; Odeyemi, Isaac; Toumi, Mondher

    2016-01-01

    Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients' non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients' HRQoL because of their side effects and the complex chronic medication regimen they represent. To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients' adherence to IT. Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants' responses. Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the

  3. The implementation and evaluation of cognitive milieu therapy for dual diagnosis inpatients: A pragmatic clinical trial

    DEFF Research Database (Denmark)

    Lykke, Jørn; Oestrich, I.; Austin, Stephen

    2010-01-01

    milieu therapy (CMT) among a group of dual diagnosis inpatients. CMT is an integrated treatment for both mental illness and substance abuse based on cognitive behavioral principles and carried out within a supportive inpatient environment. A convenience sample of dual diagnosis inpatients (N = 136......Dual diagnosis is chronic psychiatric condition involving serious mental illness and substance abuse. Experts recommend the integration of treatment for concurrent substance abuse and serious psychiatric problems. The following pragmatic trial examined the implementation and outcomes of cognitive...

  4. Cut-off value for absolute lymphocytes as an alternative for the immunophenotypic analysis of CD3+ T cells in the monitoring of immunosuppressive therapy with thymoglobulin

    Directory of Open Access Journals (Sweden)

    Gislaine Furlanetto

    Full Text Available Abstract Introduction: Immunosuppression of T lymphocytes is required for preventing acute rejection after transplantation and for the treatment of chronic autoimmune and inflammatory diseases. The laboratory monitoring for this therapy is the measurement of T cells by immunophenotyping, aiming the target value of less than 20 cells per µL. Objective: To establish a cut-off point for the total number of lymphocytes in the automated blood cell count that reflects less than twenty T cells µL by immunophenotyping. Methods: We studied and evaluated 242 kidney transplant patients that had results of automated blood cell count and quantification of T cells by immunophenotyping technique. The patients were divided into two groups, depending on the T lymphocyte immunophenotyping rates established by lower and higher than 20 cells per µL. After, we evaluated the cut-off point for lymphocytes in the blood cell count with a specificity of 100% to exclude patients with high levels of T lymphocytes. Results: We found that the cut-off point of 70 lymphocytes per µL obtained by automated blood cell count showed 100% of specificity to exclude patients with T-cell counts higher than 20 cells per µL by immunophenotyping. Conclusion: The results found in this study may be helpful to monitor the immunosuppressive therapy in kidney transplant patients in places where a flow cytometer is not available, or when this equipment is not present in the full routine.

  5. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

    Science.gov (United States)

    Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

    2003-09-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited

  6. Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction

    DEFF Research Database (Denmark)

    Green, Anders; Pottegård, Anton; Broe, Anne;

    2016-01-01

    OBJECTIVES: The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. DESIGN: A registry-based observational cohort study was performed using antecedent data. SETTING...

  7. Dual antiplatelet therapy with prasugrel or ticagrelor versus clopidogrel in interventional cardiology

    DEFF Research Database (Denmark)

    Clemmensen, Peter; Dridi, Nadia Paarup; Holmvang, Lene

    2013-01-01

    For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater effica...

  8. Systematic review of the clinical impact of dual antiplatelet therapy discontinuation after acute coronary syndromes.

    Science.gov (United States)

    Zeymer, Uwe; Becher, Anja; Jennings, Em; Johansson, Saga; Westergaard, Mogens

    2017-09-01

    The aim of this systematic literature review was to assess the consequences of dual antiplatelet therapy discontinuation on clinical outcomes after acute coronary syndromes. A systematic literature search was conducted in PubMed to identify studies reporting data on patients who discontinued dual antiplatelet therapy (planned or unplanned) following acute coronary syndromes and on the clinical impact of dual antiplatelet therapy discontinuation. To be included, more than 50% of the study population had to have had acute coronary syndrome as their index event or, if less than 50%, outcomes data must have been reported separately for the group with acute coronary syndromes. Thirty publications covering 29 studies were identified for inclusion. There was much heterogeneity across studies regarding the included patient populations, treatment durations and outcome definitions and ascertainments. Dual antiplatelet therapy discontinuation was most commonly based on physician decision. Twenty-six studies reported that clopidogrel was prescribed as part of dual antiplatelet therapy. Dual antiplatelet therapy duration was positively associated with a lower risk of all-cause mortality (seven/eight studies), cardiovascular mortality (two/two studies), non-fatal myocardial infarction (two/three studies) and stent thrombosis (five/five studies) in patients and/or patient subgroups in studies without randomised treatment designs, although such associations were not observed in the one study that randomly assigned patients to treatment (i.e. planned discontinuation). Results from our systematic literature review generally support the benefit of longer-term dual antiplatelet therapy after acute coronary syndromes; however, further research is needed to determine the optimal length of dual antiplatelet therapy in patients after acute coronary syndrome, ideally using prospective studies.

  9. The implementation and evaluation of cognitive milieu therapy for dual diagnosis inpatients: A pragmatic clinical trial

    DEFF Research Database (Denmark)

    Lykke, Jørn; Oestrich, Irene; Austin, Stephen;

    2010-01-01

    Dual diagnosis is chronic psychiatric condition involving serious mental illness and substance abuse. Experts recommend the integration of treatment for concurrent substance abuse and serious psychiatric problems. The following pragmatic trial examined the implementation and outcomes of cognitive...... milieu therapy (CMT) among a group of dual diagnosis inpatients. CMT is an integrated treatment for both mental illness and substance abuse based on cognitive behavioral principles and carried out within a supportive inpatient environment. A convenience sample of dual diagnosis inpatients (N = 136...... reported significant reductions in levels of anxiety and depressive symptoms (p dual diagnosis populations and warrants further...

  10. Concurrent Epstein-Barr virus associated NK/T cell lymphoma after immunosuppressive therapy for aplastic anemia: report of a case and review of literature.

    Science.gov (United States)

    Yin, Guangli; Ni, Ying; Xiao, Zhengrui; He, Guangsheng; Miao, Kourong

    2015-01-01

    Aplastic anemia (AA) patients with prolonged immunosuppression have a risk of development of lymphoproliferative disorders (LPDs), especially combined with Epstein-Barr virus (EBV) infection. However, development of nature killer/T (NK/T) cell lymphoma, in a nontransplantation setting, has not been documented for AA patients with immunosuppressive therapy (IST). Herein, we described a middle-aged man, Han ethnic, who presented with swelled parotid gland after a long history of IST for AA. Fever, night sweating, weight loss had not been found. Increased heterotypic lymphocytes had been detected in the left side of parotid gland demonstrated as cCD3(+), CD56(+), GranB(+), TIA-1(+), MUM-1(+), KI-67 (50%-75%)(++), Bcl-6(-), MPO(-) by immunohistochemistry, and in-situ hybridization (ISH) indicated EBER positive. Chromosome analysis by R banding method revealed 46, XY [20]. NK/T cell lymphoma concurrent with aplastic anemia was diagnosed and a mild chemotherapy regimen including vincristine, prednisone, L-asparaginase was administered. The parotid mass was gradually regressed after the first cycle of chemotherapy. The patient discharged from the hospital voluntarily and lost the follow-up.

  11. Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy

    Science.gov (United States)

    Jones, Douglas W.; Goodney, Philip P.; Conrad, Mark F.; Nolan, Brian W.; Rzucidlo, Eva M.; Powell, Richard J.; Cronenwett, Jack L.; Stone, David H.

    2016-01-01

    Objective Controversy persists regarding the perioperative management of clopidogrel among patients undergoing carotid endarterectomy (CEA). This study examined the effect of preoperative dual antiplatelet therapy (aspirin and clopidogrel) on in-hospital CEA outcomes. Methods Patients undergoing CEA in the Vascular Quality Initiative were analyzed (2003–2014). Patients on clopidogrel and aspirin (dual therapy) were compared with patients taking aspirin alone preoperatively. Study outcomes included reoperation for bleeding and thrombotic complications defined as transient ischemic attack (TIA), stroke, or myocardial infarction. Secondary outcomes were in-hospital death and composite stroke/death. Univariate and multivariable analyses assessed differences in demographics and operative factors. Propensity score-matched cohorts were derived to control for subgroup heterogeneity. Results Of 28,683 CEAs, 21,624 patients (75%) were on aspirin and 7059 (25%) were on dual therapy. Patients on dual therapy were more likely to have multiple comorbidities, including coronary artery disease (P therapy were also more likely to have a drain placed (P therapy was independently associated with increased reoperation for bleeding (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20–2.42; P = .003) but was protective against TIA or stroke (OR, 0.61; 95% CI, 0.43–0.87; P = .007), stroke (OR, 0.63; 95% CI, 0.41–0.97; P = .03), and stroke/death (OR, 0.66; 95% CI, 0.44–0.98; P = .04). Propensity score matching yielded two groups of 4548 patients and showed that patients on dual therapy were more likely to require reoperation for bleeding (1.3% vs 0.7%; P = .004) but less likely to suffer TIA or stroke (0.9% vs 1.6%; P = .002), stroke (0.6% vs 1.0%; P = .04), or stroke/death (0.7% vs 1.2%; P = .03). Within the propensity score-matched groups, patients on dual therapy had increased rates of reoperation for bleeding regardless of carotid symptom status. However, asymptomatic

  12. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Muduma G

    2016-01-01

    Full Text Available Gorden Muduma,1 Francis C Shupo,2 Sophie Dam,3 Natalia A Hawken,3 Samuel Aballéa,3 Isaac Odeyemi,1 Mondher Toumi4 1Astellas Pharma Europe Ltd, Chertsey, 2Creativ-Ceutical Ltd, London, UK; 3Creativ-Ceutical Ltd, Paris, 4Public Health (EA 3279, Faculty of Medicine, Aix-Marseille University, Marseille, France Background: Renal transplantation (RT is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients’ non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients’ HRQoL because of their side effects and the complex chronic medication regimen they represent. Purpose: To elicit key concepts related to adherence to immunosuppressant therapy (IT and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients’ adherence to IT. Materials and methods: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants’ responses. Results: Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember

  13. Comparison between spousal donor transplantation treated with anti-thymocyte globulin induction therapy and, living related donor transplantation treated with standard immunosuppression

    Directory of Open Access Journals (Sweden)

    Erkan Demir

    2014-01-01

    Full Text Available The worldwide shortage of organs available for transplantation has led to the use of living-unrelated kidney donors. In this context, spouses represent an important source of organ donors. We compared the allograft outcomes of spousal donor transplantation (SDT with anti-thymocyte globulin (ATG induction therapy and living related donor transplantation (LRDT with triple immonosuppression and basiliximab, in addition. Among the 335 living and deceased donor kidney transplantations performed between April 2001 and June 2010, there were 274 living donor kidney transplantations including 34 SDT and 240 LRDT. The minimum follow-up period was 36 months. All recipients of SDT received ATG (1.5 mg/kg induction therapy, which was stopped five to seven days after surgery. Maintenance immunosuppression included tacrolimus (TAC, mycophenolate mofetil (MMF and prednisolone. LRDT recipients received triple immunosuppressive protocol consisting of cyclosporine or TAC, MMF and prednisolone, in addition to basiliximab. There was a significant difference between the two groups in recipient age, while pre-operative duration on dialysis, recipient sex and donor age and sex were not significantly different. There was also a significant difference between the two groups in the number of human leukocyte antigen (HLA mismatches. The 1-, 3- and 5-year graft survival rates of SDT were 94.1%, 88.2% and 79.4%, respectively, and the frequency of acute rejection episodes was 5.8% (two cases. The 1-, 3- and 5-year graft survival rates of LRDT were 95.8%, 91.6% and 83.3%, respectively, with the frequency of acute rejection being 16.2%. The graft survival rates of SDT were as good as LRDT, while the acute rejection rates in SDT were lower than in LRDT, although the difference was not statistically different (P = 0.13.

  14. Systematic Review and Meta-analysis of Dual Versus Single Antiplatelet Therapy in Carotid Interventions.

    Science.gov (United States)

    Barkat, M; Hajibandeh, S; Hajibandeh, S; Torella, F; Antoniou, G A

    2017-01-01

    The importance of antiplatelet therapy for the management and prevention of ischaemic stroke cannot be overstated. Despite the established guidelines, there is no clear consensus on how to manage antiplatelet therapy during and after carotid interventions. The objective was to undertake a systematic literature review and perform a meta-analysis to assess the effects of dual antiplatelet therapy in carotid endarterectomy (CEA) and stenting (CAS). Electronic information sources (MEDLINE, EMBASE, CINAHL, CENTRAL) and bibliographic reference lists were searched to identify randomised controlled trials (RCTs) and observational studies reporting comparative outcomes of dual versus single antiplatelet therapy in CEA and CAS. Primary outcomes were mortality and stroke within 30 days of intervention. Secondary outcomes were transient ischaemic attack (TIA), major bleeding, groin or neck haematoma, and myocardial infarction (MI). Dichotomous outcome measures were reported using the risk difference (RD) and 95% confidence interval (CI). Combined overall treatment effects were calculated using fixed-effect or random-effects models. Three RCTs and seven observational studies were identified reporting a total of 36,881 CEAs and 150 CAS procedures. In CEA, there were no differences in stroke/TIA/death between single and dual antiplatelet therapy, but there was a significant risk of major bleeding (RD, 0.00; 95% CI, 0.00-0.01; p = .0003) and neck haematoma with dual therapy (RD, 0.04; 95% CI, 0.01-0.06; p = .001). In addition, the rate of MI was higher in the dual therapy group than the single therapy group (RD, 0.00; 95% CI, 0.00-0.01; p = .003). In CAS, there was no difference in major bleeding or haematoma formation, but a significant difference in TIA in favour of dual therapy was identified (RD -0.13, 95% CI, -0.22 to -0.05; p = .003). Dual antiplatelet therapy demonstrates advantages over single therapy only in CAS, as indicated by a reduced risk of TIA. Dual

  15. Dual Antiplatelet Therapy (DAPT) versus No Antiplatelet Therapy and Incidence of Major Bleeding in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Staudacher, Dawid L; Biever, Paul M; Benk, Christoph; Ahrens, Ingo; Bode, Christoph; Wengenmayer, Tobias

    2016-01-01

    Bleeding is a frequent complication in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). An indication for dual antiplatelet therapy due to coronary stent implantation is present in a considerable number of these patients. The objective of this retrospective study was to evaluate if dual antiplatelet therapy (DAPT) significantly increases the high intrinsic bleeding risk in patients on VA-ECMO. A total of 93 patients were treated with VA-ECMO between October 2010 and October 2013. Average time on VA-ECMO was 58.9 ± 1.7 hours. Dual antiplatelet therapy was given to 51.6% of all patients. Any bleeding was recorded in 60.2% of all patients. There was no difference in bleeding incidence in patients on DAPT when compared to those without any antiplatelet therapy including any bleeding (66.7% vs. 57.1%, p = 0.35), BARC3 bleeding (43.8% vs. 33.3%, p = 0.31) or pulmonary bleeding (16.7% vs. 19.0%, p = 0.77). This holds true after adjustment for confounders. Rate of transfusion of red blood cells were similar in patients with or without DAPT (35.4% vs. 28.6%, p = 0.488). Bleeding on VA-ECMO is frequent. This registry recorded no statistical difference in bleeding in patients on dual antiplatelet therapy when compared to no antiplatelet therapy. When indicated, DAPT should not be withheld from VA ECMO patients.

  16. Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Giuseppe Tarantino

    2016-10-01

    Full Text Available Background: Hepatocellular Carcinoma (HCC represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV and C (HCV viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity. We decided to review the literature to clarify the oncological role of mTORi after liver transplantation for HCC, analyzing both present condition and future perspectives.Material and Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language in the period of time between January 2005 and December 2015. Results: The literature search yielded 93 articles; after duplicates were removed, 77 titles and abstracts were reviewed. Most relevant data and papers are herein reported and discussed.Conclusions: So far, the use of mTORi is encouraging in terms of oncological outcomes for patients underwent LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited.

  17. Fibrillary glomerulonephritis with small fibrils in a patient with the antiphospholipid antibody syndrome successfully treated with immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Tagboto Senyo

    2007-05-01

    Full Text Available Abstract Background Fibrillary glomerulonephritis is a rare cause of progressive renal dysfunction, often leading to the need for dialysis within a few years. The role of immunosuppressive treatment is still uncertain although this has been tried with variable success. Case presentation A 56 year old woman with the antiphospholipid antibody syndrome (IgM anticardiolipin antibodies was seen in the nephrology clinic with haematuria, proteinuria, and worsening renal function. A renal biopsy demonstrated a mesangial proliferative glomerulonephritis on light microscopy and smaller fibrils (10.6–13.8 nm in diameter than is usual for fibrillary glomerulonephritis (typically 18–22 nm on electron microscopy. Amyloidosis was excluded following detailed evaluation. On account of rapidly worsening renal failure she was started on cyclophosphamide and prednisolone which led to the partial recovery and stabilization of her renal function. Conclusion This case highlights the need for routine electron microscopy in native renal biopsies, where the differential diagnosis is wide and varied and the light and immunofluorescence microscopic findings may be non specific.

  18. Oncological Impact of M-Tor Inhibitor Immunosuppressive Therapy after Liver Transplantation for Hepatocellular Carcinoma: Review of the Literature

    Science.gov (United States)

    Tarantino, Giuseppe; Magistri, Paolo; Ballarin, Roberto; Di Francia, Raffaele; Berretta, Massimiliano; Di Benedetto, Fabrizio

    2016-01-01

    Background: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV) and C (HCV) viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT) is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi) for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity. We decided to review the literature to clarify the oncological role of mTORi after liver transplantation for HCC, analyzing both present condition and future perspectives. Material and Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language in the period of time between January 2005 and December 2015. Results: The literature search yielded 93 articles; after duplicates were removed, 77 titles and abstracts were reviewed. Most relevant data and papers are herein reported and discussed. Conclusions: So far, the use of mTORi is encouraging in terms of oncological outcomes for patients underwent LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited. PMID:27818634

  19. Association between endothelial and platelet function markers and adiponectin in renal transplanted recipients on cyclosporine and tacrolimus immunosuppression based therapy.

    Science.gov (United States)

    Sahin, Garip; Akay, Olga Meltem; Uslu, Sema; Bal, Cengiz; Yalcin, Ahmet Ugur; Gulbas, Zafer

    2015-06-01

    Coagulation abnormalities, endothelial dysfunction and arteriosclerosis play a key role in cardiovascular disease state observed in transplanted patients. Plasma adiponectin levels are lower following kidney transplantation. However, there is still a debate about this topic in the literature. This study evaluated, adiponectin levels associated with markers of endothelial dysfunction and platelet function in renal transplant patients. Sixty-six renal transplant patients were studied. Patients were grouped according to immunosuppression regimen. Group 1 (n = 36) were treated with cyclosporine A based regimes and group 2 (n = 30) were treated with tacrolimus based regimes. Plasma adiponectin, asymmetric dimethyl arginine (ADMA), sP-selectin levels and platelet aggregation tests were studied and were compared with those in control group (n = 15, group 3). Adiponectin, sP-selectin and ADMA levels were higher in group 1 and statistically significant differences were observed compared with those of group 2 and group 3, respectively (P  0.05). Adiponectin levels are elevated in line with ADMA and sP-selectin levels. Since CsA induces higher adiponectin levels, platelet activation and endothelial dysfunction. These changes may be responsible for the increased risk of post-transplant cardiovascular events in renal transplant patients. © 2015 Asian Pacific Society of Nephrology.

  20. Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis.

    Science.gov (United States)

    Elmariah, Sammy; Mauri, Laura; Doros, Gheorghe; Galper, Benjamin Z; O'Neill, Kelly E; Steg, Philippe Gabriel; Kereiakes, Dean J; Yeh, Robert W

    2015-02-28

    Treatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders. We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death. Including the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone. Extended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy. None. Copyright © 2015

  1. Long-term outcome of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy.

    Science.gov (United States)

    Escher, Felicitas; Kühl, Uwe; Lassner, Dirk; Poller, Wolfgang; Westermann, Dirk; Pieske, Burkert; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2016-12-01

    To analyze the long-term outcome after immunosuppressive treatment of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy (CMi). We investigated 114 patients with endomyocardial biopsy (EMB)-proven virus-negative chronic myocarditis or CMi, who were treated with prednisone and azathioprine for 6 months. Myocardial inflammation was assessed by quantitative immunohistology. We examined hemodynamic measurements after 6 months and long-term follow-up periods of up to 10 years {median 10.5 months [95 % confidence interval (CI) 11.69-59.16]}. At follow-up, the patients showed a significant improvement of left ventricular ejection fraction (LVEF) compared to baseline after 6-month period (LVEF rising from 44.6 ± 17.3 to 51.8 ± 15.5 %, p = 0.006) and in the long-term follow-up (LVEF 52.1 ± 15.6 %, p = 0.006). Simultaneously, EMB-analysis revealed significant reduction of quantified inflammatory infiltrates (CD3(+) cells 16.03 ± 29.09-8.2 ± 9.0/mm(2), p = 0.002; CD2(+) cells 12.62 ± 20.01 to 6.61 ± 8.47/mm(2), p = 0.001; perforin(+) cells 3.94 ± 4.65-1.03 ± 1.47/mm(2), p = 0.0001), and cell-adhesion molecule HLA-1 [9.91 ± 5.55-6.65 ± 2.81/area fraction (AF), p = 0.0001]. In a subgroup analysis, patients with initial LVEF ≤45 % (n = 53) significantly increased with LVEF at follow-up (29.3 ± 8.8-41.7 ± 13.2-42.1 ± 13.1 %, p 45-60 % (n = 25) significantly improved further or recovered completely, regarding LVEF (53.0 ± 3.6-59.0 ± 9.4-59.8 ± 10.0 %, p = 0.03, Group II). Patients with initial LVEF >60 % (n = 36) remained stable and did not deteriorate over long-term follow-up (68.8 ± 6.7-67.5 ± 10.9-68.8 ± 10.7 %, p = 0.5, Group III). Groups II and III were defined as chronic myocarditis. In patients with virus-negative chronic myocarditis or CMi, we could show the effectiveness and beneficial effects of immunosuppressive treatment. Based on the

  2. [(11)C]DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model.

    Science.gov (United States)

    Xie, Lin; Yamasaki, Tomoteru; Ichimaru, Naotsugu; Yui, Joji; Kawamura, Kazunori; Kumata, Katsushi; Hatori, Akiko; Nonomura, Norio; Zhang, Ming-Rong; Li, Xiao-Kang; Takahara, Shiro

    2012-03-01

    Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7-[(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE.

  3. Overview of immunosuppression in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Anjana A Pillai; Josh Levitsky

    2009-01-01

    Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate periand post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.

  4. Cancer immunotherapy by immunosuppression

    Directory of Open Access Journals (Sweden)

    Prehn Liisa M

    2010-12-01

    Full Text Available Abstract We have previously suggested that the stimulatory effect of a weak immune reaction on tumor growth may be necessary for the growth of incipient tumors. In the present paper, we enlarge upon and extend that idea by collecting evidence in the literature bearing upon this new hypothesis that a growing cancer, whether in man or mouse, is throughout its lifespan, probably growing and progressing because of continued immune stimulation by a weak immune reaction. We also suggest that prolonged immunosuppression might interfere with progression and thus be an aid to therapy. While most of the considerable evidence that supports the hypothesis comes from observations of experimental mouse tumors, there is suggestive evidence that human tumors may behave in much the same way, and as far as we can ascertain, there is no present evidence that necessarily refutes the hypothesis.

  5. Fluorescence and Magnetic Resonance Dual-Modality Imaging-Guided Photothermal and Photodynamic Dual-Therapy with Magnetic Porphyrin-Metal Organic Framework Nanocomposites

    Science.gov (United States)

    Zhang, Hui; Li, Yu-Hao; Chen, Yang; Wang, Man-Man; Wang, Xue-Sheng; Yin, Xue-Bo

    2017-01-01

    Phototherapy shows some unique advantages in clinical application, such as remote controllability, improved selectivity, and low bio-toxicity, than chemotherapy. In order to improve the safety and therapeutic efficacy, imaging-guided therapy seems particularly important because it integrates visible information to speculate the distribution and metabolism of the probe. Here we prepare biocompatible core-shell nanocomposites for dual-modality imaging-guided photothermal and photodynamic dual-therapy by the in situ growth of porphyrin-metal organic framework (PMOF) on Fe3O4@C core. Fe3O4@C core was used as T2-weighted magnetic resonance (MR) imaging and photothermal therapy (PTT) agent. The optical properties of porphyrin were well remained in PMOF, and PMOF was therefore selected for photodynamic therapy (PDT) and fluorescence imaging. Fluorescence and MR dual-modality imaging-guided PTT and PDT dual-therapy was confirmed with tumour-bearing mice as model. The high tumour accumulation of Fe3O4@C@PMOF and controllable light excitation at the tumour site achieved efficient cancer therapy, but low toxicity was observed to the normal tissues. The results demonstrated that Fe3O4@C@PMOF was a promising dual-imaging guided PTT and PDT dual-therapy platform for tumour diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity. PMID:28272454

  6. When a Single Antiplatelet Agent for Stroke Prevention Is Not Enough: Current Evidence and Future Applications of Dual Antiplatelet Therapy.

    Science.gov (United States)

    Yuan, Kristy; Kim, Anthony S

    2016-04-01

    For secondary stroke prevention, long-term dual antiplatelet therapy is not recommended due to increased bleeding risks. There is no specific evidence for using dual antiplatelet therapy for cervical artery dissection or for adding a second antiplatelet agent after a stroke while taking aspirin monotherapy. For patients with atrial fibrillation and stroke/TIA unable to tolerate warfarin, aspirin monotherapy is reasonable. Dual antiplatelet therapy carries a similar risk of major bleeding as warfarin that offsets reductions in stroke risk. Dual antiplatelet therapy is recommended for endovascular cerebrovascular stenting procedures, although the optimal duration of therapy is not well established. Short-term dual antiplatelet therapy when initiated acutely after minor stroke/TIA, particularly in Asian populations or for intracranial atherosclerosis, holds promise though studies to evaluate this approach more generally are ongoing. New antiplatelet agents and additional data on the pharmacogenetics of clopidogrel metabolism have the potential to help to individualize these recommendations moving forward.

  7. Contact lens intolerance: refitting with dual axis lens for corneal refractive therapy

    Science.gov (United States)

    López-López, María; Pelegrín-Sánchez, José Miguel; Sobrado-Calvo, Paloma; García-Ayuso, Diego

    2011-01-01

    Corneal refractive therapy is a non-surgical procedure whose main purpose is to improve uncorrected visual acuity during the day, without spectacles or contact lenses. We report an adult woman who shows contact lens intolerance and does not want to wear eyeglasses. We used dual axis contact lens to improve lens centration. We demonstrate a maintained unaided visual acuity during one year of treatment. In conclusion, we can consider refitting with dual axis lens for corneal refractive therapy as a non-surgical option for patients who show contact lens intolerance.

  8. Music Therapy Interventions for Deaf Clients with Dual Diagnosis

    OpenAIRE

    Anna Johnson Ward

    2016-01-01

    The current music therapy literature addresses the use of music with the Deaf population, particularly those with cochlear implants. However, few studies or descriptions of music therapy with Deaf individuals who are dually diagnosed with an emotional or behavioral disorder and an intellectual disability have been conducted. Given that music therapy has been found to be an effective intervention for both Deaf individuals and individuals with emotional or behavioral needs, ideas and resources ...

  9. Extended Duration Dual Antiplatelet Therapy After Coronary Stenting Among Patients With Peripheral Arterial Disease: A Subanalysis of the Dual Antiplatelet Therapy Study.

    Science.gov (United States)

    Secemsky, Eric A; Yeh, Robert W; Kereiakes, Dean J; Cutlip, Donald E; Steg, P Gabriel; Massaro, Joseph M; Apruzzese, Patricia K; Mauri, Laura

    2017-05-08

    This study sought to determine whether patients with peripheral arterial disease (PAD) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD. Patients with PAD have increased ischemic and bleeding risks after coronary stenting. The DAPT (Dual Antiplatelet Therapy) study randomized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone. The effects of continued thienopyridine on myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (death, MI, or stroke) and bleeding (GUSTO [Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries] moderate or severe) were assessed among those with versus without PAD. Among 11,648 randomized patients, 649 (5.57%) had PAD. Between 12 and 30 months, randomized patients with PAD had higher rates of MI/stent thrombosis (6.03% vs. 2.92%; p antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among Men Who Have Sex With Men in the Netherlands

    NARCIS (Netherlands)

    Xiridou, Maria; Lugnér, Anna; De Vries, Henry J C; Van Bergen, Jan E A M; Götz, Hannelore M.; Van Benthem, Birgit H B; Wallinga, Jacco; Van Der Sande, Marianne A B

    2016-01-01

    BACKGROUND: In response to the rising threat of resistance to first-line antibiotics for gonorrhea, international guidelines recommend dual antimicrobial therapy. However, some countries continue to recommend monotherapy. We assess the cost-effectiveness of dual therapy with ceftriaxone and azithrom

  11. Professional Identity Perceptions of Dual-Prepared Art Therapy Graduates

    Science.gov (United States)

    Feen-Calligan, Holly R.

    2012-01-01

    This article describes a qualitative study of the development of professional identity in art therapists who also prepare as counselors. Graduates from one university's two distinct master's degree programs were interviewed: (a) art therapy (n = 9) and (b) art therapy combined with counseling (n = 11). Most participants regardless of their degree…

  12. Professional Identity Perceptions of Dual-Prepared Art Therapy Graduates

    Science.gov (United States)

    Feen-Calligan, Holly R.

    2012-01-01

    This article describes a qualitative study of the development of professional identity in art therapists who also prepare as counselors. Graduates from one university's two distinct master's degree programs were interviewed: (a) art therapy (n = 9) and (b) art therapy combined with counseling (n = 11). Most participants regardless of their degree…

  13. Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma.

    Science.gov (United States)

    Siurala, Mikko; Havunen, Riikka; Saha, Dipongkor; Lumen, Dave; Airaksinen, Anu J; Tähtinen, Siri; Cervera-Carrascon, Víctor; Bramante, Simona; Parviainen, Suvi; Vähä-Koskela, Markus; Kanerva, Anna; Hemminki, Akseli

    2016-08-01

    Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFα, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of (111)In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies.

  14. Alternative dosing of dual PI3K and MEK inhibition in cancer therapy

    Directory of Open Access Journals (Sweden)

    Jokinen Elina

    2012-12-01

    Full Text Available Abstract Background PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways are thought to be the central transducers of oncogenic signals in solid malignancies, and there has been a lot of enthusiasm for developing inhibitors of these pathways for cancer therapy. Some preclinical models have suggested that combining inhibitors of both parallel pathways may be more efficacious, but it remains unknown whether dual inhibition with high enough concentrations of the drugs to achieve meaningful target inhibition is tolerable in a clinical setting. Furthermore, the predictive factors for dual inhibition are unknown. Methods Non-small cell lung cancer (NSCLC cell lines (n=12 with the most frequent oncogenic backgrounds (K-Ras mut n=3, EGFR mut n=3, ALK translocated n=3, and triple-negative n=3 were exposed to PI3K inhibitors (ZSTK474, PI-103 or MEK inhibitor (CI-1040 alone or in combination and analysed with an MTS growth/cytotoxicity assay and statistically by combination index analysis. The activity of the intracellular signaling pathways in response to the inhibitor treatments was analysed with a western blot using phospho-specific antibodies to AKT, ERK1/2, S6, and 4E-BPI. For the differential dosing schedule experiments, additional breast and colon cancer cell lines known to be sensitive to dual inhibition were included. Results Two of the 12 NSCLC cell lines tested, H3122 (ALK translocated and H1437 (triple-negative, showed increased cytotoxicity upon dual MEK and PI3K inhibition. Furthermore, MDA-MB231 (breast and HCT116 (colon, showed increased cytotoxicity upon dual inhibition, as in previous studies. Activation of parallel pathways in the dual inhibition-sensitive lines was also noted in response to single inhibitor treatment. Otherwise, no significant differences in downstream intracellular pathway activity (S6 and 4E-BPI were noted between PI3K alone and dual inhibition other than the increased cytotoxicity of the latter. In the alternative dosing

  15. X-band Linac for a 6 MeV dual-head radiation therapy gantry

    Science.gov (United States)

    Lee, Seung Hyun; Shin, Seung-Wook; Lee, Jongchul; Kim, Hui-Su; Lee, Byeong-No; Lee, Byung-Chul; Park, Hyung-dal; Song, Ki-back; Song, Ho-seung; Mun, Sangchul; Ha, Donghyup; Chai, Jong-Seo

    2017-04-01

    We developed a design for a 6 MeV X-band linear accelerator for radiation therapy in a dual-head gantry layout. The dual-head gantry has two linacs that can be operated independently. Each X-band linac accelerates electron bunches using high-power RF and generates X-rays for radiation therapy. It requires a versatile RF system and pulse sequence to accomplish various radiation therapy procedures. The RF system consists of 9.3 GHz, 2 MW X-band magnetron and associated RF transmission components. A test linac was assembled and operated to characterize its RF performance without beam. This paper presents these results along with a description of the gantry linacs and their operational requirements.

  16. An RF Therapy System for Breast Cancer Using Dual Deformable Mirrors — Computational Study

    Science.gov (United States)

    Arunachalam, Kavitha; Udpa, Satish S.; Udpa, Lalita

    2007-03-01

    Breast cancer is the second leading cause of cancer deaths amongst women in the United States. In the past two decades, the potential of non-ionizing high power RF waves to destroy cancerous biological tissues is actively investigated for cancer therapy. This paper presents the computational feasibility study of an alternative mode of electromagnetic radiation therapy that employs dual source and deformable mirror. The adaptive focusing capability of the deformable mirror is exploited for preferential energy deposition at the tumor site in the breast irradiated by electromagnetic radiation. The outcome of the computational study for the proposed deformable mirror-based thermal therapy for breast cancer is presented in this paper.

  17. Preclinical animal research on therapy dosimetry with dual isotopes

    NARCIS (Netherlands)

    M.W. Konijnenberg (Mark); M. de Jong (Marion)

    2011-01-01

    textabstractPreclinical research into radionuclide therapies based on radiation dosimetry will enable the use of any LET-equivalent radionuclide. Radiation dose and dose rate have significant influence on dose effects in the tumour depending on its radiation sensitivity, possibilities for repair of

  18. Preclinical animal research on therapy dosimetry with dual isotopes

    NARCIS (Netherlands)

    M.W. Konijnenberg (Mark); M. de Jong (Marion)

    2011-01-01

    textabstractPreclinical research into radionuclide therapies based on radiation dosimetry will enable the use of any LET-equivalent radionuclide. Radiation dose and dose rate have significant influence on dose effects in the tumour depending on its radiation sensitivity, possibilities for repair of

  19. Safety and efficacy of a raltegravir-based dual antiretroviral therapy in clinical practice

    Directory of Open Access Journals (Sweden)

    G Cenderello

    2012-11-01

    Full Text Available Background: HAART has revolutionized HIV disease management and increased life expectancy for most HIV-infected individuals on treatment. A nucleoside/tide reverse transcriptase (NRTI inhibitor backbone is a recommended component of standard first-line HAART. Nevertheless, NRTI-sparing alternatives are warranted in order to reduce long-term toxicities in many patients (pts. Aim of the study was to evaluate safety of raltegravir-based dual antiretroviral therapy (DUAL in a clinical practice setting. Methods: All pts on DUAL regimen followed at our outpatient HIV service on May 31st 2012 were recruited. Their clinical files were retrospectively studied. Collected data included: demographics, CDC staging, reason to DUAL switching, cholesterol (total and HDL, creatinine, CK, CD4+ count and HIV RNA were recorded at switch and every six months after for the first year. Change in CD4 count after the switch was evaluated by Student t-test. Results: The cohort included 55 pts (27 M; mean age was 54 years (38–72. HIV infection was acquired through: injective drug abuse (25, unprotected homosexual (24 and heterosexual (16 intercourse. CDC staging was: A=16, B=26, C=13. Mean previous treatment regimens were 4. At time of study pts had been on DUAL regimen for 23 months. They had been switched to DUAL therapy for: drug resistance (14; 25.5% (DRR or drug toxicity (41; 74.5%. The most frequently associated drug was darunavir/rtv (19; 34.5%, followed by atazanavir (13; 23.6%; 5 were unboosted; lopinavir/rtv (12; 21.8%, and NVP (11; 20%. DRR pts presented at baseline a mean viral load of 40,153 copies of HIV-RNA/ml; after at 12 months all but 3 showed undetectable (<40 copies viral load and a mean CD4 gain of 142 cells/ml. Pts switched to DUAL for toxicity presented persistent undetectable viral load and a mean CD4+gain of 94 cells/ml. The observed CD4+ increase in both groups (DRR and toxicity presented a statistical significance (p<0.01. Total and HDL

  20. STUDENTS AND FACULTY MEMBERS IN MARRIAGE AND FAMILY THERAPY PROGRAMS: NAVIGATING SUCCESSFUL NON-SEXUAL DUAL RELATIONSHIPS

    OpenAIRE

    2004-01-01

    Dual relationships in the family therapy field are currently under debate. Within this debate extreme viewpoints and opinions, on what is the best way to navigate dual relationships, are being voiced. These views range from avoiding non-sexual dual relationships at all costs to glorifying the possibilities of such a relationship. To obtain a snap shot of faculty and student experiences a web survey was sent to fifteen masters and ten doctoral COAMFTE-accredited programs. Participants were 76 ...

  1. Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction.

    Science.gov (United States)

    Yeh, Robert W; Kereiakes, Dean J; Steg, Philippe Gabriel; Windecker, Stephan; Rinaldi, Michael J; Gershlick, Anthony H; Cutlip, Donald E; Cohen, David J; Tanguay, Jean-Francois; Jacobs, Alice; Wiviott, Stephen D; Massaro, Joseph M; Iancu, Adrian C; Mauri, Laura

    2015-05-26

    The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Midazolam-ketamine dual therapy stops cholinergic status epilepticus and reduces Morris water maze deficits.

    Science.gov (United States)

    Niquet, Jerome; Baldwin, Roger; Norman, Keith; Suchomelova, Lucie; Lumley, Lucille; Wasterlain, Claude G

    2016-09-01

    Pharmacoresistance remains an unsolved therapeutic challenge in status epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE triggers a rapid internalization of synaptic γ-aminobutyric acid A (GABAA ) receptors and externalization of N-methyl-d-aspartate (NMDA) receptors that may explain the loss of potency of standard antiepileptic drugs (AEDs). We hypothesized that a drug combination aimed at correcting the consequences of receptor trafficking would reduce SE severity and its long-term consequences. A severe model of SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAA receptor agonist midazolam, the NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min after SE onset in combination or as monotherapy. Measures of SE severity were the primary outcome. Secondary outcomes were acute neuronal injury, spontaneous recurrent seizures (SRS), and Morris water maze (MWM) deficits. Midazolam-ketamine dual therapy was more efficient than double-dose midazolam or ketamine monotherapy or than valproate-midazolam or valproate-ketamine dual therapy in reducing several parameters of SE severity, suggesting a synergistic mechanism. In addition, midazolam-ketamine dual therapy reduced SE-induced acute neuronal injury, epileptogenesis, and MWM deficits. This study showed that a treatment aimed at correcting maladaptive GABAA receptor and NMDA receptor trafficking can stop SE and reduce its long-term consequences. Early midazolam-ketamine dual therapy may be superior to monotherapy in the treatment of benzodiazepine-refractory SE. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy

    Science.gov (United States)

    Guimarães, Juliana Rodrigues; Melgaço, Juliana Gil; Kevorkian, Yohan Britto; Bottino, Fernanda de Oliveira; Vieira, Yasmine Rangel; da Silva, Aline Campos de Azevedo; Pinto, Douglas Pereira; da Fonseca, Laís Bastos; Vilhena, Leandro Schiavo; Uiechi, Edilson; da Silva, Maria Cristina Carlan; Moran, Julio; Marchevsky, Renato Sérgio; Cruz, Oswaldo Gonçalves; Otonel, Rodrigo Alejandro Arellano; Alfieri, Amauri Alcindo; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pinto, Marcelo Alves

    2017-01-01

    Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis

  4. 儿童肾移植术后的免疫抑制治疗%Comparison of the immunosuppressive therapies for kidney transplantation in children

    Institute of Scientific and Technical Information of China (English)

    杨顺良; 谭建明; 吴卫真; 林文洪; 徐廷昭; 蔡锦全; 陶小琴; 王庆华; 王栋; 高霞

    2008-01-01

    ,azathioprine and steroid:and group E received Tacrolimus,MMF and steroid.Results The recipient/graft survival rates after 1,3,and 5 years were 100%/97%,91%/87.8% and 84.4%/80.9% respectively.The survival rates of Cyclosporine-based and Tacrolimus-based immunosuppression at 1,3 and 5 year were 48.5%/51.5%,60%/40% and 53.6/43.4% respectively.The survival rates for azathioprine and MMF group were 21.2%/78.8%,23.3%/70%,32.1%/60.7% respectively.The dosage of Cyclosporine was 2~3 mg·kg-1·d-1,with the trough levels between 100 ng/mL to 150 ng/mL.When Tacrolimus was used,the dosage was 0.03~O.05 mg·kg-1·d-1,with its trough level rangmg from 1.5 ng/mL to 3 ng/mL.There were no significant difference of the dosage and blood for Cyclos porine or Tacrolimus at different period.The dosage of MMF was 10 mg·kg-1·d-1,and prednisone was 5~1 0 mg/d.The incompliance rate was 30%,and 5 patients lost their renal grafts,of which one suffered from rejection and four died with normal renal function,2 from pulmonary infection,and 2 from drug induced liver impairment.The other complications included:hypertension 35.7%,hyper lipidemia 28.6%,infection 17.9%,gingival hyperplasia 14.3%,hypertrichiasis 10.7%,and diabetes mellitus 3.6%. Conclusions Cyctosporine/Tacrolimus,MMF,plus prednisone regimen is the most effective immunosuppressive therapy for pediatric renal recipients.

  5. Overcoming immunosuppression in bone metastases.

    Science.gov (United States)

    Reinstein, Zachary Z; Pamarthy, Sahithi; Sagar, Vinay; Costa, Ricardo; Abdulkadir, Sarki A; Giles, Francis J; Carneiro, Benedito A

    2017-09-01

    Bone metastases are present in up to 70% of advanced prostate and breast cancers and occur at significant rates in a variety of other cancers. Bone metastases can be associated with significant morbidity. The establishment of bone metastasis activates several immunosuppressive mechanisms. Hence, understanding the tumor-bone microenvironment is crucial to inform the development of novel therapies. This review describes the current standard of care for patients with bone metastatic disease and novel treatment options targeting the microenvironment. Treatments reviewed include immunotherapies, cryoablation, and targeted therapies. Combinatorial treatment strategies including targeted therapies and immunotherapies show promise in pre-clinical and clinical studies to overcome the suppressive environment and improve treatment of bone metastases. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. A green approach to dual-drug nanoformulations with targeting and synergistic effects for cancer therapy.

    Science.gov (United States)

    Wu, Shichao; Yang, Xiangrui; Lu, Yue; Fan, Zhongxiong; Li, Yang; Jiang, Yuan; Hou, Zhenqing

    2017-11-01

    Exploration of efficient dual-drug nanohybrids, particularly those with high drug loading, specific targeting property, and long-termed stability, is of highly importance in cancer therapy. A pH-driven coprecipitation was performed in the aqueous phase to obtain a dual-drug nanoformulation, composed of 10-hydroxycamptothecine (HCPT) nanoneedles integrated with an exterior thin layer of the methotrexate (MTX)-chitosan conjugate. The high stability of nanohybrids in water and the targeting property provided by the MTX ingredient function synergistically to the prolonged and sustained drug release property in tumor tissues and the increased cellular uptake. The cytotoxicity test illustrates that dual-drug nanoneedles possess the remarkable killing ability to HeLa cells with the combination index at 0.33 ± 0.07. After cellular internalization, the release of both drug ingredients results in an excellent anticancer activity in vivo with the minimized adverse side effects. Design of a green approach to the carrier-free, dual-drug nanoformulations enables to develop emerging drug delivery systems for cancer diagnosis and treatment.

  7. WE-A-BRF-01: Dual-Energy CT Imaging in Diagnostic Imaging and Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Molloi, S [University of California, Irvine, CA (United States); Li, B [Boston University Medical Center, Boston, MA (United States); Yin, F [Duke University Medical Center, Durham, NC (United States); Chen, H [New York Presbyterian Hospital, New York, NY (United States)

    2014-06-15

    classification based on calcium scores shows excellent agreement with classification on the basis of conventional coronary artery calcium scoring. These studies demonstrate dual-energy cardiovascular CT can potentially be a noninvasive and sensitive modality in high risk patients. On-board KV/MV Imaging. To enhance soft tissue contrast and reduce metal artifacts, we have developed a dual-energy CBCT technique and a novel on-board kV/MV imaging technique based on hardware available on modern linear accelerators. We have also evaluated the feasibility of these two techniques in various phantom studies. Optimal techniques (energy, beam filtration, # of overlapping projections, etc) have been investigated with unique calibration procedures, which leads to successful decomposition of imaged material into acrylic-aluminum basis material pair. This enables the synthesis of virtual monochromatic (VM) CBCT images that demonstrate much less beam hardening, significantly reduced metal artifacts, and/or higher soft tissue CNR compared to single-energy CBCT. Adaptive Radiation Therapy. DECT could actually contribute to the area of Dose-Guided Radiation Therapy (or Adaptive Therapy). The application of DECT imaging using 80kV and 140 kV combinations could potentially increase the image quality by reducing the bone or high density material artifacts and also increase the soft tissue contrast by a light contrast agent. The result of this higher contrast / quality images is beneficial for deformable image registration / segmentation algorithm to improve its accuracy hence to make adaptive therapy less time consuming in its recontouring process. The real time re-planning prior to per treatment fraction could become more realistic with this improvement especially in hypofractional SBRT cases. Learning Objectives: Learn recent developments of dual-energy imaging in diagnosis and radiation therapy; Understand the unique clinical problem and required quantification accuracy in each application

  8. Dental extraction without stopping single or dual antiplatelet therapy: results of a retrospective cohort study.

    Science.gov (United States)

    Lu, S-Y; Tsai, C-Y; Lin, L-H; Lu, S-N

    2016-10-01

    The aim of this study was to investigate the incidence of bleeding after dental extraction without stopping antiplatelet therapy. Postoperative bleeding was assessed in a total of 1271 patients who were divided into two groups: a study group comprising 183 patients on antiplatelet therapy (aspirin 125 patients/185 occasions; clopidogrel 42 patients/65 occasions; dual therapy 16 patients/24 occasions) who underwent 548 dental extractions on 274 occasions, and a control group comprising 1088 patients who were not receiving any antiplatelet or anticoagulant therapy and underwent 2487 dental extractions on 1472 occasions. The incidence of postoperative bleeding was higher in the study group (5/274, 1.8%) than in the control group (10/1472, 0.7%), and also in the dual antiplatelet subgroup (1/24, 4.2%) than in the single antiplatelet subgroups (clopidogrel: 2/65, 3.1%; aspirin: 2/185, 1.1%); however, these differences were not significant. Postoperative bleeding was managed successfully by repacking with Gelfoam impregnated with tranexamic acid powder in 12 patients and by resuturing in three of the control patients undergoing extraction of impacted teeth with flap elevation. These findings indicate that there is no need to interrupt antiplatelet drugs before dental extraction. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. [Traveling with immunosuppression].

    Science.gov (United States)

    Birkenfeld, G

    2014-03-01

    The rapidly increasing number of patients with immunosuppression is followed by their expectation to lead-as much as possible-a "normal" life, including long-distance travel. The advice and preventive measures for diseases associated with travelling depend overall on the mode of the patient's immunosuppression. This report explains the individual preventive possibilities, limits and risks for travellers with asplenia, common variable immunodeficiency, chronic inflammatory bowel and rheumatic diseases, HIV, as well as for patients having undergone solid organ or bone marrow transplantation or chemotherapy.

  10. Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

    Institute of Scientific and Technical Information of China (English)

    Toshihiro Nishizawa; Hidekazu Suzuki; Takama Maekawa; Naohiko Harada; Tatsuya Toyokawa; Toshio Kuwai; Masanori Ohara

    2012-01-01

    We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy.In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen,a third-line eradication regimen with mbeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk.Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy.A total of 46 patients were included; however,two were lost to followup.The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively.The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil,respectively.The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P =0.019).A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%.Adverse effects were reported in 18.2% of the patients,mainly diarrhea and stomatitis.Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

  11. Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy.

    Science.gov (United States)

    Baumgartner, Bernhard; Draxler, Wolfgang; Lewis, Kevin M

    2016-12-01

    The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. Twenty-eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in life-threatening bleeding of 35-292 ml/min. In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC.

  12. Comparison of on-treatment platelet reactivity between triple antiplatelet therapy with cilostazol and standard dual antiplatelet therapy in patients undergoing coronary interventions: a meta-analysis.

    Science.gov (United States)

    Panchal, Hemang B; Shah, Tejaskumar; Patel, Parthavkumar; Albalbissi, Kais; Molnar, Janos; Coffey, Brandon; Khosla, Sandeep; Ramu, Vijay

    2013-11-01

    The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 µmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 µmol/L (MD: -14.4, CI: -21.6 to -7.2, P antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.

  13. Cutaneous malignancies in immunosuppressed organ transplant recipients.

    Science.gov (United States)

    Seda, Ivette M Sosa; Zubair, Adeel; Brewer, Jerry D

    2014-01-01

    During the past century, organ transplantation has delivered the miracle of life to more than 500,000 patients in need. Secondary malignancies have developed as an unforeseen consequence of intense immunosuppressive regimens. Cutaneous malignancies have been recognized as the most frequent cancer that arises post-transplantation. Among organ transplant recipients (OTRs), skin cancer is a substantial cause of morbidity and potential mortality. The authors discuss epidemiology and clinical presentation of cutaneous malignancies; associated risk factors; recommendation for the care of immunosuppressed OTRs, and emerging therapies on the horizon.

  14. Optimization of dual-energy CT acquisitions for proton therapy using projection-based decomposition.

    Science.gov (United States)

    Vilches-Freixas, Gloria; Létang, Jean Michel; Ducros, Nicolas; Rit, Simon

    2017-09-01

    Dual-energy computed tomography (DECT) has been presented as a valid alternative to single-energy CT to reduce the uncertainty of the conversion of patient CT numbers to proton stopping power ratio (SPR) of tissues relative to water. The aim of this work was to optimize DECT acquisition protocols from simulations of X-ray images for the treatment planning of proton therapy using a projection-based dual-energy decomposition algorithm. We have investigated the effect of various voltages and tin filtration combinations on the SPR map accuracy and precision, and the influence of the dose allocation between the low-energy (LE) and the high-energy (HE) acquisitions. For all spectra combinations, virtual CT projections of the Gammex phantom were simulated with a realistic energy-integrating detector response model. Two situations were simulated: an ideal case without noise (infinite dose) and a realistic situation with Poisson noise corresponding to a 20 mGy total central dose. To determine the optimal dose balance, the proportion of LE-dose with respect to the total dose was varied from 10% to 90% while keeping the central dose constant, for four dual-energy spectra. SPR images were derived using a two-step projection-based decomposition approach. The ranges of 70 MeV, 90 MeV, and 100 MeV proton beams onto the adult female (AF) reference computational phantom of the ICRP were analytically determined from the reconstructed SPR maps. The energy separation between the incident spectra had a strong impact on the SPR precision. Maximizing the incident energy gap reduced image noise. However, the energy gap was not a good metric to evaluate the accuracy of the SPR. In terms of SPR accuracy, a large variability of the optimal spectra was observed when studying each phantom material separately. The SPR accuracy was almost flat in the 30-70% LE-dose range, while the precision showed a minimum slightly shifted in favor of lower LE-dose. Photon noise in the SPR images (20 mGy dose

  15. Precise Photodynamic Therapy of Cancer via Subcellular Dynamic Tracing of Dual-loaded Upconversion Nanophotosensitizers

    Science.gov (United States)

    Chang, Yulei; Li, Xiaodan; Zhang, Li; Xia, Lu; Liu, Xiaomin; Li, Cuixia; Zhang, Youlin; Tu, Langping; Xue, Bin; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

    2017-01-01

    Recent advances in upconversion nanophotosensitizers (UCNPs-PS) excited by near-infrared (NIR) light have led to substantial progress in improving photodynamic therapy (PDT) of cancer. For a successful PDT, subcellular organelles are promising therapeutic targets for reaching a satisfactory efficacy. It is of vital importance for these nanophotosensitizers to reach specifically the organelles and to perform PDT with precise time control. To do so, we have in this work traced the dynamic subcellular distribution, especially in organelles such as lysosomes and mitochondria, of the poly(allylamine)-modified and dual-loaded nanophotosensitizers. The apoptosis of the cancer cells induced by PDT with the dependence of the distribution status of the nanophotosensitizers in organelles was obtained, which has provided an in-depth picture of intracellular trafficking of organelle-targeted nanophotosensitizers. Our results shall facilitate the improvement of nanotechnology assisted photodynamic therapy of cancers. PMID:28361967

  16. A supramolecular material for dual-modal imaging and targeted cancer therapy.

    Science.gov (United States)

    Guan, Shanyue; Liang, Ruizheng; Li, Chunyang; Wei, Min

    2017-04-01

    Recently, how to design a formulation system with simultaneous diagnosis and therapy toward cancer has attracted tremendous attention. Herein, a supramolecular material was prepared via a facile method by the co-intercalation of folic acid (FA) and doxorubicin (DOX) into the gallery of Gd(3+)-doped layered double hydroxides (LDHs), followed by surface adsorption of fluorescein isothiocyanate (FITC). This supramolecular agent was proved to exhibit excellent magnetic resonance imaging (MRI) and fluorescence imaging (FI) behavior, as well as chemotherapy toward cancer (KB cell). The co-intercalated FA enables an efficient and selective drug delivery with good specificity. This work provides a facile approach for the fabrication of a drug formulation with dual-modal imaging and targeted therapy, which could be potentially used in the practical chemotherapy and medical imaging.

  17. Manualized treatment for substance abusers with personality disorders: dual focus schema therapy.

    Science.gov (United States)

    Ball, S A

    1998-01-01

    The presence of an untreated personality disorder may be associated with worse compliance and outcome in substance abuse treatment. Therapeutic attention to the symptoms of personality disorder may reduce the severity of substance abuse and other Axis I symptoms which potentially contribute to relapse. A 24-week manual-guided individual cognitive-behavioral therapy approach has been developed that integrates relapse prevention with targeted intervention for early maladaptive schemas (enduring negative beliefs about oneself, others, and events) and coping styles. This Dual Focus Schema Therapy is being compared to 12-Step Drug Counseling for opioid-dependent individuals with personality disorders in an ongoing study funded by the National Institute on Drug Abuse. This article reviews Young's (1994) schema-focused theory and approach and summarizes the treatment manual, which integrates relapse prevention for substance abuse.

  18. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  19. Dual-phase dual-energy CT in patients with lung cancer: assessment of the additional value of iodine quantification in lymph node therapy response

    Energy Technology Data Exchange (ETDEWEB)

    Baxa, Jan; Vondrakova, Alena; Matouskova, Tana; Ferda, Jiri [Charles University Teaching Hospital Plzen, Department of Imaging Methods, Plzen (Czech Republic); Ruzickova, Olga [Charles University Teaching Hospital Plzen, Department of Pulmonary Diseases, Plzen (Czech Republic); Schmidt, Bernhard; Flohr, Thomas; Sedlmair, Martin [Siemens Healthcare, CT Physics and Applications Development, Forchheim (Germany)

    2014-08-15

    To investigate the potential contribution of iodine uptake calculation from dual-phase dual-energy CT (DE-CT) for lymph node staging and therapy response monitoring in lung cancer patients. Retrospective analysis of 27 patients with non-small cell lung carcinoma (NSCLC), who underwent dual-phase DE-CT before and after chemotherapy, was performed. Iodine uptake (mg/mL) and total iodine uptake (mg) were calculated using prototype software in the early (arterial) and late (venous) post-contrast circulatory phase in 110 mediastinal lymph nodes. The arterial enhancement fraction (AEF) was calculated and compared with lymph node size and response to chemotherapy. A significant difference of AEF was observed between enlarged (90.4 %; 32.3-238.5 %) and non-enlarged (72.7 %; -37.5-237.5 %) lymph nodes (p = 0.044) before treatment onset. A significantly different change of AEF in responding (decrease of 26.3 %; p = 0.022) and non-responding (increase of 43.0 %; p = 0.031) lymph nodes was demonstrated. A higher value of AEF before treatment was observed in lymph nodes with subsequent favourable response (88.6 % vs. 77.7 %; p = 0.122), but this difference did not reach statistical significance. The dual-phase DE-CT examination with quantification of ratio of early and late post-contrast iodine uptake is a feasible and promising method for the functional evaluation of mediastinal lymph nodes including therapy response assessment. (orig.)

  20. May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

    Science.gov (United States)

    Tontodonati, Monica; Cento, Valeria; Polilli, Ennio; Colabattista, Cecilia; Cascella, Raffaella; Sciotti, Mariapina; Di Giammartino, Dante; Trave, Francesca; Di Maio, Velia Chiara; Monarca, Roberto; Di Candilo, Francesco; Prinapori, Roberta; Rastrelli, Elena; Vecchiet, Jacopo; Ceccherini-Silberstein, Francesca; Manzoli, Lamberto; Giardina, Emiliano; Perno, Carlo Federico; Parruti, Giustino

    2015-10-01

    When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

  1. A network meta-analysis of the efficacy of belatacept, cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients.

    Science.gov (United States)

    Goring, Sarah M; Levy, Adrian R; Ghement, Isabella; Kalsekar, Anupama; Eyawo, Oghenowede; L'Italien, Gilbert J; Kasiske, Bertram

    2014-08-01

    Belatacept is a first in-class co-stimulation blocker developed for primary maintenance immunosuppression following renal transplantation. The objective of this study was to estimate the efficacy of belatacept relative to tacrolimus and cyclosporine among adults receiving a single kidney transplant. A systematic review was conducted of randomized clinical trials (RCTs) published between January 1990 and December 2013 using EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, and unpublished study reports from two belatacept RCTs. Bayesian network meta-analysis (NMA) methods were used to compare the efficacy measures, mortality, graft loss, acute rejection and glomerular filtration rate (GFR). Heterogeneity was quantified using statistical metrics and potential sources were evaluated using meta-regression and subgroup analysis. A total of 28 RCTs comparing tacrolimus with cyclosporine, and three comparing belatacept with cyclosporine, were identified. All three agents provided comparable graft and patient survival, despite a higher risk of acute rejection associated with belatacept and cyclosporine. Belatacept was associated with significant improvement in GFR versus cyclosporine. Compared with tacrolimus, this difference was clinically meaningful yet statistically non-significant. The probability of being the best treatment was highest for belatacept for graft survival (68%), patient survival (97%) and renal function (89%), and highest for tacrolimus for acute rejection (99%).Variability in donor, recipient, and trial characteristics was present in the included RCTs; however, minimal statistical heterogeneity was detected in the analysis of acute rejection, graft or patient survival, and none of the characteristics were found to be significantly associated with relative effect. Although the direction of effect of immunosuppressants on GFR was consistent across RCTs, precise estimation of its magnitude was limited by a small number of RCTs and

  2. Dual antiplatelet therapy and the severity risk of lower intestinal bleeding

    Directory of Open Access Journals (Sweden)

    Neal Carlin

    2017-01-01

    Full Text Available Background: Dual antiplatelet (Plt therapy with aspirin and clopidogrel is recommended for up to 1 year following acute coronary syndrome. Many of these cardiac patients are also on anithrombotic therapy like warfarin. Lower gastrointestinal bleeding (LGIB is the main adverse event of this treatment. Aims: The main purpose of this study was to analyze the relationship of dual anti-Plt therapy and the risk of LGIB. Methods: Patients' electronic charts were reviewed to include a total of 19 variables, which included age, sex, ethnicity, daily use aspirin of any dose, daily use of clopidogrel, use of nonsteroidal anti-infl ammatory drugs (NSAIDs at least twice in the last week prior to admission and the daily use of anticoagulants (warfarin, heparin, and were obtained from history and physical examination reports, lab transcripts and procedural reports. Settings/Design: A retrospective cohort study of the records of 3436 patients admitted to our hospital from January 1, 2009, to December 31, 2011, was evaluated. All the patients included were admitted through the emergency department with complaints of or relating to LGIB. The primary outcome studied was severe LGIB as defined by the requirement of at least two units of packed red blood cells and/or a decrease in the hematocrit of 20% or more or recurrent bleeding after 24 h of clinical stability with additional transfusions required. Other outcomes included surgical intervention. Statistical Methods/Analysis: Univariate analysis using t-test on continuous variables and Chi-square test on categorical variables were done before carrying out logistic regression analysis. Logistic regression analyses were conducted to measures of association between the variables and LGIB. Logistic regression analysis was not carried for surgical intervention and death because none of the variables was significant from univariate tests. Results: A total of 511 patients were found to have true LGIB. Among these

  3. Immunosuppression for islet transplantation.

    Directory of Open Access Journals (Sweden)

    Noguchi,Hirofumi

    2006-04-01

    Full Text Available The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen is a significant breakthrough that allows the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year ; however, the rate is reduced to 50% at 3 years, attributed to prolonged tacrolimus exposure. Recently, immunosuppression agents such as cyclosporine, mycophenolate mofetil, and the novel agent FTY 720 have been used instead of tacrolimus. Lymphocytedepleting antibodies such as anti-thymocyte globulin, alemtuzumab, and hOKT3gamma 1 (ala, ala have been launched, and a costimulatory blockade of anti-CD40 monoclonal antibodies and CTLA4-Ig will be attempted in the near future. Moreover, the potential of a novel immunosuppressing peptide could now be realized using new technology called the protein transduction system. In this review, we show some of the most recent contributions to the advancement of knowledge in this field.

  4. Tumor Microenvironment and Angiogenic Blood Vessels Dual-Targeting for Enhanced Anti-Glioma Therapy.

    Science.gov (United States)

    Hu, Quanyin; Kang, Ting; Feng, Jingxian; Zhu, Qianqian; Jiang, Tianze; Yao, Jianhui; Jiang, Xinguo; Chen, Jun

    2016-09-14

    Advances in active targeting drug delivery system (DDS) have revolutionized glioma diagnosis and therapy. However, the lack of the sufficient targets on glioma cells and limited penetration capability of DDS have significantly compromised the treatment efficacy. In this study, by taking advantages of the abundant extracellular matrix-derived heparan sulfate proteoglycan (HSPG) and enhanced tumor penetration ability mediated by neuropilin-1 (NRP-1) protein, we reported the ATWLPPR and CGKRK peptide dual-decorated nanoparticulate DDS (designated AC-NP) to achieve angiogenic blood vessels and tumor microenvironment dual-targeting effect. The resulted AC-NP displayed the particle size of 123 ± 19.47 nm. Enhanced cellular association of AC-NP was achieved on HUVEC cells and U87MG cells. AC-NP was internalized via caveolin- and lipid raft-mediated mechanism with the involvement of energy and lysosome in HUVEC cells and via caveolin- and lipid raft-mediated pathway with the participation of energy, microtubulin, and lysosome in U87MG cells. After loading with anticancer drug, paclitaxel (PTX), the enhanced apoptosis induction and antiproliferative activity were achieved by AC-NP. Furthermore, in vitro U87MG tumor spheroids assays showed a deeper penetration and an enhanced inhibitory effect against the U87MG tumor spheroids achieved by AC-NP. In vivo animal experiment showed that decoration of AC peptide on the nanoparticulate DDS resulted in extensive accumulation at glioma site and improved anti-glioma efficacy. Collectively, the results suggested that AC-NP holds great promise to serve as an effective tumor blood vessel and tumor microenvironment dual-targeting DDS with enhanced penetration capability, holding great potential in improving anti-glioma efficacy.

  5. Costs associated with common dual-controller therapies for treating asthma in several managed care populations.

    Science.gov (United States)

    Legorreta, Antonio P

    2002-01-01

    To present results of 2 studies assessing the impact of 3 commonly prescribed dual-controller regimens on the cost of treating asthma in several managed care populations. Two previously published cross-sectional and longitudinal retrospective studies of patients aged 12-65 years with asthma, in selected managed care plans, who were taking an inhaled corticosteroid (ICS) and were prescribed an index prescription for salmeterol or a leukotriene modifier. The cross-sectional study showed that different drug regimens were associated with measurable differences in outcome when both drug costs and use of medical services are taken into account. This stimulated a more rigorous follow-up study controlling for asthma severity by using preindex cost and use measures. The 12-month risk-adjusted total cost for the fluticasone propionate and salmeterol group was the lowest at 975 dollars, followed by 1,089 dollars and 1,268 dollars for the ICS and salmeterol and the ICS and leukotriene modifier groups, respectively. Overall cost per patient of dual-controller therapy consisting of fluticasone propionate and the inhaled long-acting beta2-agonist salmeterol was lower than a regimen consisting of either another inhaled corticosteroid with salmeterol or an inhaled corticosteroid with a leukotriene modifier. The cost of asthma treatment failure (i.e., inpatient and emergency department) was similar between groups.

  6. Previous hypertensive hemorrhage increases the risk for bleeding and ischemia for PCI patients on dual antiplatelet therapy.

    Science.gov (United States)

    Qiao, Manli; Bi, Qi; Fu, Paul; Wang, Yixin; Song, Zhe; Guo, Fang

    2017-06-01

    The use of antiplatelet therapy after intracerebral hemorrhage remains controversial, while the use of dual antiplatelet therapy (DAPT) is required after cardiac stenting. In this study, we examine the risk of bleeding and ischemic events for PCI patients with a history of hypertensive hemorrhage on DAPT. A total of 128 cases and 153 controls were selected from Chinese patients with cardiac stenting on dual anti-platelet therapy for a single-center retrospective case-control study. Patients with a history of hypertensive hemorrhage were selected for the case group, while patients with a history of hypertension were chosen as control. All patients were on aspirin 100 mg and clopidogrel 75 mg after cardiac stenting, and were followed for a duration of 12-48 months. The primary outcomes were intracerebral hemorrhage, major bleeding, and major adverse cardiovascular and cerebrovascular events. A history of previous hypertensive hemorrhage was not found to be a risk factor for intracerebral hemorrhage and major bleeding while on dual anti-platelet therapy. However, a history of either hypertensive hemorrhage or coronary artery disease was independently found to be risk factors for major adverse cardiovascular and cerebrovascular events. On sub-group analysis, patients with a history of hypertensive hemorrhage within 12 months were found to be at higher risk for bleeding on dual anti-platelet therapy, while patients with history of hypertensive hemorrhage outside of 12 months on dual anti-platelet therapy did not have the same increased risk. A history of hypertensive hemorrhage and coronary heart disease were two independent risk factors for major adverse cardiovascular and cerebrovascular events in PCI patients taking DAPT. A history of hypertensive hemorrhage less than 12 months had an increased risk for recurrent intracerebral hemorrhage and major bleeding in PCI patients taking DAPT.

  7. Analytical validation of a quantitative reverse transcriptase polymerase chain reaction assay for evaluation of T-cell targeted immunosuppressive therapy in the dog.

    Science.gov (United States)

    Riggs, C; Archer, T; Fellman, C; Figueiredo, A S; Follows, J; Stokes, J; Wills, R; Mackin, A; Bulla, C

    2013-12-15

    Cyclosporine is an immunosuppressive agent that inhibits T-cell function by decreasing production of cytokines such as interleukin-2 (IL-2) and interferon-γ(IFN-γ). In dogs, there is currently no reliable analytical method for determining effective cyclosporine dosages in individual patients. Our laboratory has developed a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay that measures IL-2 and IFN-γ gene expression, with the goal of quantifying immunosuppression in dogs treated with cyclosporine. This study focuses on analytical validation of our assay, and on the effects of sample storage conditions on cyclosporine-exposed samples. Heparinized whole blood collected from healthy adult dogs was exposed to a typical post-treatment blood concentration for cyclosporine(500 ng/mL) for 1 h, and then stored for 0, 24, and 48 h at both room temperature and 4 ◦C.The study was then repeated using a cyclosporine concentration of 75 ng/mL, with sample storage for 0, 24, and 48 h at 4 ◦C. Cytokine gene expression was measured using RT-qPCR,and assay efficiency and inter- and intra-assay variability were determined. Storage for upto 24 h at room temperature, and up to 48 h at 4 ◦C, did not significantly alter results compared to samples that were processed immediately. Validation studies showed our assay to be highly efficient and reproducible and robust enough to be feasible under standard practice submission conditions. © 2013 Elsevier B.V. All rights reserved.

  8. Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

    Directory of Open Access Journals (Sweden)

    Jae Hyun Park

    2011-10-01

    Full Text Available Background: Progressive multifocal leukoencephalopathy (PML is a demyelinating central nervous system disease caused by JC virus (JCV reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. Case Report: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. Conclusion: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis.

  9. How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

    Science.gov (United States)

    Bagoly, Zsuzsa; Homoródi, Nóra; Kovács, Emese Gyöngyvér; Sarkady, Ferenc; Csiba, László; Édes, István; Muszbek, László

    2016-01-01

    Dual antiplatelet therapy with clopidogrel and aspirin is frequently used for the prevention of recurrent ischemic events. Various laboratory methods are used to detect the effect of these drugs administered in monotherapy, however their value in dual therapy has not been explored. Here, we determined which methods used for testing the effect of clopidogrel or aspirin are influenced by the other antiplatelet agent. One arm of the study included 53 ischemic stroke patients being on clopidogrel monotherapy showing effective inhibition of the P2Y12 ADP receptor. Laboratory tests routinely used for the detection of aspirin resistance (arachidonic acid (AA)-induced platelet aggregation/secretion, AA-induced thromboxane B2 (TXB2) production in platelet-rich plasma and VerifyNow Aspirin assay) were carried out on samples obtained from these patients. The other arm of the study involved 52 patients with coronary artery disease being on aspirin monotherapy. Methods used for testing the effect of clopidogrel (ADP-induced platelet aggregation and secretion, flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP) phosphorylation and a newly developed P2Y12-specific platelet aggregation (ADP[PGE1] test)) were performed on samples obtained from these patients. Clopidogrel monotherapy significantly inhibited AA-induced platelet aggregation and secretion, moreover, AA-induced TXB2 production was also significantly decreased. VASP phosphorylation and AA-induced platelet aggregation showed fair correlation in patients taking clopidogrel only. Clopidogrel did not inhibit the VerifyNow Aspirin test significantly. Aspirin monotherapy influenced ADP-induced platelet aggregation and secretion, but did not have an effect on VASP phosphorylation and on the ADP[PGE1] platelet aggregation test.

  10. 颅脑创伤后血清抗脑抗体变化及免疫抑制研究%A study on the changes of the antibrain - antibody and immunosuppression therapy after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    闫华; 徐鹏; 薛静; 侯永新; 段世博; 李冰; 张国斌; 刘暌; 只达石

    2010-01-01

    目的 研究重型颅脑创伤患者血清抗脑抗体变化趋势;探讨免疫抑制治疗对于创伤后兔脑组织的保护作用.方法 ELISA法检测49例颅脑创伤患者和47例健康人的血清抗脑抗体浓度,时间点为伤后第3天、第7天、2周、3周、1、2、6、9个月;24只新西兰大白兔随机分为创伤组、免疫抑制组、假手术组;免疫抑制组伤后隔日口服环孢素A 50 mg,收集创伤前2 h及伤后3、7、14、21、28、35、42、49 d血清标本,检测血清抗脑抗体的浓度;50 d后处死,取创伤周围皮层组织,用免疫组化法测定谷氨酸表达,TUNEL法测定细胞凋亡.结果 颅腩创伤患者血清抗脑抗体明显高于健康人并持续较长时间;兔免疫抑制剂组血清抗脑抗体峰值较创伤组低;三组兔血清中抗腩抗体浓度两两比较差异有统计学意义(P<0.05);免疫抑制组兔创伤周围脑组织谷氨酸表达以及凋亡细胞明显低于颅脑创伤组(P<0.05).结论 健康人群血清中存在少量抗脑抗体;颅脑创伤后血清中抗腩抗体较正常状态明显升高;免疫抑制治疗通过降低组织免疫功能,降低自身抗脑抗体的产生,从而减轻继发性脑损害;免疫抑制治疗将可能是一种新的颅脑创伤治疗方法.%Objective To study the changes of antibrain - antibody (ABAb) in patients with traumatic brain injury and to explore the cerebral protective effects of immunosuppression therapy in rabbit -TBI - models established by lateral fluid percussion machine. Methods 96 cases (Traumatic brain injury 49 case , health adults 47 case) were phlebotomized and tested with ELISA to observe the changes of ABAb at the time points 3 d,7 d, 2w, 3w, 1m,2 m, 6 m,9 m; 24 rabbits were separated into TBI group( n = 8)、sham operation group (n=8)、TBI + immunosuppression therapy group (n=8). Immunosuppression therapy group was fed with CsA (50 mg/2 d) through the tummy duct post -TBI. 3 group rabbits were phlebotomized at the time

  11. Immunosuppression by discodermolide.

    Science.gov (United States)

    Longley, R E; Gunasekera, S P; Faherty, D; Mclane, J; Dumont, F

    1993-11-30

    In summary, discodermolide, a novel, marine-derived compound, is a potent in vitro and in vivo immunosuppressive agent. Discodermolide blocks cellular proliferation in lymphoid and nonlymphoid cells. This blocking action is not due to cytotoxicity. Blockage of cell proliferation by discodermolide appears to occur at the G2/M interface of the cell cycle, similar to that observed with other types of antiproliferative drugs (i.e., doxorubicin). The cell cycle block appears to be reversible, as cells recover normal cycling patterns within 48 h after removal of the compound. Additional work with this compound is targeted towards determining the exact nature of discodermolide's mitotic block and is currently under way.

  12. Tacrolimus-induced hypertension and nephrotoxicity in Fawn-Hooded rats are attenuated by dual inhibition of renin-angiotensin system

    NARCIS (Netherlands)

    Hoskova, Lenka; Malek, Ivan; Kautzner, Josef; Honsova, Eva; van Dokkum, Richard P. E.; Huskova, Zuzana; Vojtiskova, Alzbeta; Varcabova, Sarka; Cervenka, Ludek; Kopkan, Libor

    Chronic immunosuppressive therapy is often complicated by the development of both arterial hypertension and renal dysfunction. The principal aim of this study was to assess the effects of dual inhibition of renin-angiotensin system (RAS) and other antihypertensive treatment on blood pressure and

  13. Tacrolimus-induced hypertension and nephrotoxicity in Fawn-Hooded rats are attenuated by dual inhibition of renin-angiotensin system

    NARCIS (Netherlands)

    Hoskova, Lenka; Malek, Ivan; Kautzner, Josef; Honsova, Eva; van Dokkum, Richard P. E.; Huskova, Zuzana; Vojtiskova, Alzbeta; Varcabova, Sarka; Cervenka, Ludek; Kopkan, Libor

    2014-01-01

    Chronic immunosuppressive therapy is often complicated by the development of both arterial hypertension and renal dysfunction. The principal aim of this study was to assess the effects of dual inhibition of renin-angiotensin system (RAS) and other antihypertensive treatment on blood pressure and ren

  14. A randomized, comparative study of dual therapy (doxycycline–rifampin versus triple therapy (doxycycline–rifampin–levofloxacin for treating acute/subacute brucellosis

    Directory of Open Access Journals (Sweden)

    Ahmad Hasanain

    Full Text Available Abstract Aim The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline–rifampin to a quinolone-based, triple therapy (doxycycline–rifampin–levofloxacin for treating acute/subacute brucellosis. Patients and methods We studied 107 consecutive, naïve patients with acute/subacute brucellosis admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline–rifampin (group-A or to receive the triple therapy of doxycycline–rifampin–levofloxacin (group-B. Acute/subacute brucellosis was diagnosed based on the presence of: (1 contact with animals or fresh animal products, (2 suggestive clinical manifestations of less than one-year duration, and (3 positive antibody titer (1:160 by standard tube agglutination test. Results There was no significant difference between the two groups regarding their demographic data. Fever was the most frequent manifestation (96.3%. Epigastric pain was the most frequent adverse effect of treatment (12.1%. Group-A patients had a significantly higher relapse rate compared to group-B patients (22.6% versus 9.3%, p-value = 0.01. The rate of treatment adverse effects was higher among group-B patients, although not reaching statistical significance (20.4% versus 11.3%, p-value = 0.059. Conclusions Adding levofloxacin to the dual therapy for acute/subacute brucellosis (doxycycline–rifampin may increase its efficacy in terms of lowering the relapse rate of the disease. Further, larger scale studies are needed before considering modifying the standard, dual therapy for brucellosis.

  15. Total variation superiorization in dual-energy CT reconstruction for proton therapy treatment planning

    Science.gov (United States)

    Zhu, Jiahua; Penfold, Scott

    2017-04-01

    Proton therapy is a precise form of radiotherapy in which the range of an energetic beam of protons within a patient must be accurately known. The current approach based on single-energy computed tomography (SECT) can lead to uncertainties in the proton range of approximately 3%. This range of uncertainty may lead to under-dosing of the tumour or over-dosing of healthy tissues. Dual-energy CT (DECT) theoretically has the potential to reduce these range uncertainties by quantifying electron density and the effective atomic number. In practice, however, DECT images reconstructed with filtered backprojection (FBP) tend to suffer from high levels of noise. The objective of the current work was to examine the effect of total variation superiorization (TVS) on proton therapy planning accuracy when compared with FBP. A virtual CT scanner was created with the Monte Carlo toolkit Geant4. Tomographic images were reconstructed with FBP and TVS combined with diagonally relaxed orthogonal projections (TVS-DROP). A total variation minimization (TVM) filter was also applied to the image reconstructed with FBP (FBP-TVM). Quantitative accuracy and variance of proton relative stopping power (RSP) derived from each image set was assessed. Mean RSPs were comparable with each image; however, the standard deviation of pixel values with TVS-DROP was reduced by a factor of 0.44 compared with the FBP image and a factor of 0.66 when compared with the FBP-TVM image. Proton doses calculated with the TVS-DROP image set were also better able to predict a reference dose distribution when compared with the FBP and FBP-TVM image sets. The study demonstrated the potential advantages of TVS-DROP as an image reconstruction method for DECT applied to proton therapy treatment planning.

  16. Postmenopausal women have an increased maximal platelet reactivity compared to men despite dual antiplatelet therapy.

    Science.gov (United States)

    Bobbert, Peter; Stellbaum, Caroline; Steffens, Daniel; Schütte, Claudia; Bobbert, Thomas; Schultheiss, Heinz Peter; Rauch, Ursula

    2012-12-01

    Dual antiplatelet medication with acetylsalicylic acid (ASA) and clopidogrel is the main therapy for patients with stable coronary vessel disease (CVD) after percutaneous coronary intervention (PCI). Despite platelet inhibition subgroups of patients have been shown to exhibit an increase of risk for adverse cardiovascular events. The aim of our study was to elucidate the influence of sex on platelet reactivity in patients with CVD under medication with ASA and clopidogrel. Two hundred and thirty patients with CVD on combined therapy with ASA (100 mg/day) and clopidogrel (75 mg/day) were included into our study. These patients were divided into a male (n = 128) and female (n = 102) group. Platelet reactivity was assessed by impedance aggregometry. Women demonstrated a significantly higher thrombin receptor-activating peptide (TRAP)-induced platelet reactivity than men (male 79.43 ± 28.55 U vs. female 89.3 ± 30.69 U; P 0.05) or arachidonic acid-induced (male 10.3 ± 12.87 U vs. female 12.76 ± 14.44 U; P > 0.05) platelet aggregation did not differ significantly between women and men. A multivariate linear regression model revealed female sex to be a significant prognostic marker for an increased TRAP-induced platelet reactivity, independent of the ASA and clopidogrel-associated platelet function inhibition. Sex differences did not influence the effectiveness of ASA or clopidogrel-mediated platelet function inhibition. Nevertheless, women had a significantly increased maximal platelet reactivity compared to men despite antiplatelet therapy.

  17. CpG oligodeoxynucleotides inhibit tumor growth and reverse the immunosuppression caused by the therapy with 5-fluorouracil in murine hepatoma

    Institute of Scientific and Technical Information of China (English)

    Xian-Song Wang; Zhen Sheng; You-Bing Ruan; Yang Guang; Mu-Lan Yang

    2005-01-01

    AIM: To investigate the effect of CpG-containing oligodeoxynucleotides (CpG ODN) alone or in combination with the chemotherapeutic agent 5-fluorouracil (5-FU) on tumor growth and whether CpG ODN can reverse the immunosuppression caused by the chemotherapy with 5-FU in murine hepatoma model.METHODS: Hepatoma model was established by subcutaneous inoculation with hepatoma-22 (H22) cells into the right flank of BALB/c mice. Mice with tumor were treated by peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU. Tumor size was quantified regularly. Serum levels of IL-12 and IFN-γ in mice were assayed by enzyme-linked immunosorbent assay (ELISA). The lytic capacity of splenic NK cells was tested by lactate dehydrogenase release assay.RESULTS: Peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU, and the treatment with 5-FU alone all led to significant inhibition of hepatoma growth. The mean tumor volumes fell by 46.66% in mice injected with CpG ODN, 68.34% in the 5-FU treated mice, and 70.23% in mice treated with the combination of CpG ODN and 5-FU than in controls. There was no significant difference in tumor size between 5-FUtreated mice and mice treated with the combination of 5-FU and CpG ODN (P>0.05). The serum levels of IL-12and IFN-γ of mice treated with CpG ODN alone (IL-12:464.50±24.37 pg/mL; IFN-γ:134.20±25.76 pg/mL) or with the co-administration of CpG ODN and 5-FU (IL-12:335.83±28.74 pg/mL; IFN-γ:111.00±5.33 pg/mL)were significantly higher than that of controls (IL-12:237.50±45.31 pg/mL; IFN-γ: 56.75±8.22 pg/mL). The production of IL-12 and IFN-γwas suppressed moderately in 5-FU-treated mice (IL-12:166.67±53.22 pg/mL;53.33±16.98 pg/mL) compared to control mice (P>0.05),whereas the combination of CpG ODN and 5-FU significantly increased the serum levels of IL-12 and IFN-γ compared to 5-FU alone (P<0.05). The NK cell killing activity in CpG ODNtreated mice (44.04

  18. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K;

    2000-01-01

    Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV...... seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-alpha in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART....

  19. A dual energy CT study on vascular effects of gold nanoparticles in radiation therapy

    Science.gov (United States)

    Ashton, Jeffrey R.; Hoye, Jocelyn; Deland, Katherine; Whitley, Melodi; Qi, Yi; Moding, Everett; Kirsch, David G.; West, Jennifer; Badea, Cristian T.

    2016-03-01

    Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and CT imaging. AuNPs are delivered to tumors via the enhanced permeability and retention effect and they preferentially accumulate in close proximity to the tumor blood vessels. AuNPs produce low-energy, short-range photoelectrons during external beam radiation therapy (RT), boosting dose. This work is focused on understanding how tumor vascular permeability is influenced by AuNP-augmented radiation therapy (RT), and how this knowledge can potentially improve the delivery of additional nanoparticle-based chemotherapeutics. We use dual energy (DE) CT to detect accumulation of AuNPs and increased vascular permeability to liposomal iodine (i.e. a surrogate for chemotherapeutics with liposome encapsulation) following RT. We used sarcoma tumors generated in LSL-KrasG12D; p53FL/FL conditional mutant mice. A total of n=37 mice were used in this study. The treated mice were injected with 20 mg AuNP (0.1 ml/25 g mouse) 24 hours before delivery of 5 Gy RT (n=5), 10 Gy RT (n=3) or 20 Gy RT (n=6). The control mice received no AuNP injection and either no RT (n=6), 5 Gy RT (n=3), 10 Gy RT (n=3), 20 Gy RT (n=11). Twenty four hours post-RT, the mice were injected with liposomal iodine (0.3 ml/25 mouse) and imaged with DE-CT three days later. The results suggest that independent of any AuNP usage, RT levels of 10 Gy and 20 Gy increase the permeability of tumor vasculature to liposomal iodine and that the increase in permeability is dose-dependent. We found that the effect of RT on vasculature may already be at its maximum response i.e. saturated at 20 Gy, and therefore the addition of AuNPs had almost no added benefit. Similarly, at 5 Gy RT, our data suggests that there was no effect of AuNP augmentation on tumor vascular permeability. However, by using AuNPs with 10 Gy RT, we observed an increase in the vascular permeability, however this is not yet statistically significant due to the small

  20. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K;

    2000-01-01

    Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV-infec...

  1. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Garred, Peter

    2013-01-01

    increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent......A markedly increased risk of cervical cancer is known in women immunosuppressed due to AIDS or therapy following organ transplantation. The aim of this review is to determine the association between other conditions affecting the immune system and the risk of cervical cancer. Patients with end......-stage renal disease seem to be at an increased risk of cervical cancer. A higher risk of cervical precancerous lesions was found in patients with some autoimmune diseases; particularly if treated with immunosuppressants. Among behavioral factors weakening the immune system, smoking appeared to strongly...

  2. Pulmonary alveolar hemorrhage mimicking a pneumopathy: a rare complication of dual antiplatelet therapy for ST elevation myocardial infarction

    Science.gov (United States)

    Oualim, Sara; Elharda, Charafeddine Ait; Benzeroual, Dounia; Hattaoui, Mustapha El

    2016-01-01

    Diffuse alveolar hemorrhage after percutaneous coronary intervention (PCI) is a rare complication. The diagnosis is difficult and can mimic by clinical and radiological features other diagnosis as pneumopathy. We herein report the case of a 63-year-old female admitted to the hospital for ST elevation myocardial infarction. The patient underwent PCI and received dual antiplatelet therapy. Four days later, she developed dyspnea, hemoptysis and fever. Clinical, radiological and biological findings oriented to a pneumopathy and the patient received the treatment for it. Later and because of the non improvement, a thoracic computed tomography was performed and revealed patchy areas of ground-glass opacity consistent with a diffuse pulmonary hemorrhage. The combination therapy with aspirin and clopidogrel was therefore the most likely cause. Although the dual antiplatelet combination reduces systemic ischemic events after PCI, it is associated with increased risk of nonfatal and sometimes fatal bleeding. Hence the necessity of close and careful observation to watch for possible fatal complications.

  3. Duration of Dual Antiplatelet Therapy in Coronary Artery Disease: a Review Article.

    Science.gov (United States)

    Moseley, Alex D; Collado, Fareed M; Volgman, Annabelle Santos; Schaer, Gary L; Snell, R Jeffrey

    2016-07-01

    Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines.

  4. Thermal responsive micelles for dual tumor-targeting imaging and therapy

    Science.gov (United States)

    Chen, Haiyan; Li, Bowen; Qiu, Jiadan; Li, Jiangyu; Jin, Jing; Dai, Shuhang; Ma, Yuxiang; Gu, Yueqing

    2013-11-01

    Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.

  5. Gold Nanocage-Photosensitizer Conjugates for Dual-Modal Image-Guided Enhanced Photodynamic Therapy

    Science.gov (United States)

    Srivatsan, Avinash; Jenkins, Samir V.; Jeon, Mansik; Wu, Zhijin; Kim, Chulhong; Chen, Jingyi; Pandey, Ravindra K.

    2014-01-01

    We have demonstrated that gold nanocage-photosensitizer conjugates can enable dual image-guided delivery of photosensitizer and significantly improve the efficacy of photodynamic therapy in a murine model. The photosensitizer, 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide (HPPH), was noncovalently entrapped in the poly(ethylene glycol) monolayer coated on the surface of gold nanocages. The conjugate is stable in saline solutions, while incubation in protein rich solutions leads to gradual unloading of the HPPH, which can be monitored optically by fluorescence and photoacoustic imaging. The slow nature of the release in turn results in an increase in accumulation of the drug within implanted tumors due to the passive delivery of gold nanocages. Furthermore, the conjugate is found to generate more therapeutic singlet oxygen and have a lower IC50 value than the free drug alone. Thus the conjugate shows significant suppression of tumor growth as compared to the free drug in vivo. Short-term study showed neither toxicity nor phenotypical changes in mice at therapeutic dose of the conjugates or even at 100-fold higher than therapeutic dose of gold nanocages. PMID:24465274

  6. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Geeganage, Chamila M; Diener, Hans-Christoph; Algra, Ale; Chen, Christopher; Topol, Eric J; Dengler, Reinhard; Markus, Hugh S; Bath, Matthew W; Bath, Philip M W

    2012-04-01

    Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI). Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49-0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56-0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56-0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86-5.06). Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.

  7. Review papers immunosuppressive treatment

    Directory of Open Access Journals (Sweden)

    Anna Kryś

    2014-03-01

    Full Text Available Sebaceous carcinoma (sebaceous gland carcinoma – SC is a very aggressive malignant skin tumor that arises from the epithelium of sebaceous glands. Sun exposure and long-term immunosuppression, mainly in organ transplant recipients, are the most common risk factors. The tumor was first well described by Allaire in 1891. Sebaceous carcinoma is rare and accounts for less than 1% of all cutaneous malignancies and from 1% to 5.5% of all eyelid malignancies. The most common localization is the eyelids, where it derives from the Meibomian and Zeiss glands. Most cases occur in woman between 60 and 80 years of age, but the tumor can be seen at any age, even in childhood. It appears mostly as a small, slowly growing, painless and firm mass, sometimes as a small yellowish plaque or ulceration. SC has a tendency for local recurrence and distant metastases. The local recurrence rate ranges from 9 to 36% and tends to appear within the first 5 years from diagnosis. The most effective method of treatment is surgical excision (Mohs’ microsurgical excision if it is possible. The rate of metastases is about 14-25%. The sites of metastases are usually lymph nodes, liver, lungs, bones, and brain. The mortality rate is about 22% but it increases to 50% at 5 years in patients with metastatic disease.

  8. A simulation study of a dual-plate in-room PET system for dose verification in carbon ion therapy

    CERN Document Server

    Chen, Ze; Xiao, Guo-Qing; Chen, Jin-Da; Zhang, Xiu-Ling; Guo, Zhong-Yan; Sun, Zhi-Yu; Huang, Wen-Xue; Wang, Jian-Song

    2013-01-01

    Carbon ion therapy have the ability to overcome the limitation of convertional radiotherapy due to its most energy deposition in selective depth, usually called Bragg peak, which results in increased biological effectiness. During carbon ion therapy, lots positron emitters such as $^{11}$C, $^{15}$O, $^{10}$C are generated in irradiated tissues by nuclear reactions. Immediately after patient irradiation, PET scanners can be used to measure the spatial distribution of positron emitters, which can track the carbon beam to the tissue. In this study, we designed and evaluated an dual-plate in-room PET scanner to monitor patient dose in carbon ion therapy, which is based on GATE simulation platform. A dual-plate PET is designed to avoid interference with the carbon beam line and with patient positioning. Its performance was compared with that of four-head and full-ring PET scanners. The dual-plate, four-head and full-ring PET scanners consisted of 30, 60, 60 detector modules, respectively, with a 36 cm distance be...

  9. Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple negative breast cancer cell model.

    Directory of Open Access Journals (Sweden)

    Cornelia Braicu

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG. RT2Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment.

  10. Gastroscopy-related adverse cardiac events and bleeding complications among patients treated with coronary stents and dual antiplatelet therapy

    DEFF Research Database (Denmark)

    Egholm, Gro; Thim, Troels; Madsen, Morten

    2016-01-01

    BACKGROUND AND STUDY AIMS: Dual antiplatelet therapy (DAPT) is recommended following percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DAPT is a risk factor for gastrointestinal bleeding. We aimed to quantify (1) the rate of gastroscopy within 12 months after PCI, (2) the rate...... of adverse cardiac events and gastroscopy-related bleeding complications within 30 days of gastroscopy, and (3) the association between antiplatelet therapy and these events. PATIENTS AND METHODS: Patients receiving gastroscopy within 12 months of PCI were identified and two nested case-control analyses were...

  11. Toward the definition of immunosuppressive regimens with antitumor activity.

    Science.gov (United States)

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  12. A simulation study of a dual-plate in-room PET system for dose verification in carbon ion therapy

    Science.gov (United States)

    Chen, Ze; Hu, Zheng-Guo; Chen, Jin-Da; Zhang, Xiu-Ling; Guo, Zhong-Yan; Xiao, Guo-Qing; Sun, Zhi-Yu; Huang, Wen-Xue; Wang, Jian-Song

    2014-08-01

    During carbon ion therapy, lots of positron emitters such as 11C, 15O, 10C are generated in irradiated tissues by nuclear reactions, and can be used to track the carbon beam in the tissue by a positron emission tomography (PET) scanner. In this study, an dual-plate in-room PET scanner has been designed and evaluated based on the GATE simulation platform to monitor patient dose in carbon ion therapy. The dual-plate PET is designed to avoid interference with the carbon beamline and with patient positioning. Its performance was compared with that of four-head and full-ring PET scanners. The dual-plate, four-head and full-ring PET scanners consisted of 30, 60, 60 detector modules, respectively, with a 36 cm distance between directly opposite detector modules for dose deposition measurements. Each detector module consisted of a 24×24 array of 2 mm×2 mm×18 mm LYSO pixels coupled to a Hamamatsu H8500 PMT. To estimate the production yield of positron emitters, a 10 cm×15 cm×15 cm cuboid PMMA phantom was irradiated with 172, 200, 250 MeV/u 12C beams. 3D images of the activity distribution measured by the three types of scanner are produced by an iterative reconstruction algorithm. By comparing the longitudinal profile of positron emitters along the carbon beam path, it is indicated that use of the dual-plate PET scanner is feasible for monitoring the dose distribution in carbon ion therapy.

  13. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

    2013-10-01

    Dual-antiplatelet regimens for prevention of recurrent stroke promote antithrombotic effects but may increase the risk for hemorrhage. To qualitatively and quantitatively examine the risk for recurrent stroke and intracranial hemorrhage (ICH) linked to long-term dual- and single-antiplatelet therapy among patients with ischemic stroke and transient ischemic attack. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials through March 2013 without language restrictions. The search identified 7 randomized, controlled trials that involved a total of 39,574 participants and reported recurrent stroke and ICH as outcome measures. All data from eligible studies were independently abstracted by 2 investigators according to a standard protocol. Recurrent stroke risk did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to 1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among patients receiving dual-antiplatelet therapy than among those receiving clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]). Agents used in dual- and single-antiplatelet therapies varied across trials, and the relatively modest number of trials limited subgroup analysis. Compared with monotherapy, dual-antiplatelet therapy lasting more than 1 year after an index ischemic stroke or transient ischemic attack is not associated with a greater reduction in overall recurrent stroke risk. However, long-term dual-antiplatelet therapy is linked to higher risk for ICH than clopidogrel monotherapy in this patient population. Chang Gung Memorial Hospital.

  14. Optimal duration of dual antiplatelet therapy following percutaneous coronary intervention: protocol for an umbrella review

    Science.gov (United States)

    Kelly, Shannon E; Bai, Zemin; Liu, Wenfei; Skidmore, Becky; Boucher, Michel; So, Derek Y F; Wells, George A

    2017-01-01

    Introduction Although dual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting, the optimal duration is unknown. Recent evidence indicates there may be benefits in extending the duration beyond 12 months but such decisions may increase the risk of bleeding. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review assessing the optimal duration of DAPT. Methods and analysis We will perform a comprehensive search of the published and grey literature for systematic reviews involving randomised controlled trials (RCTs) assessing the optimal duration of DAPT following PCI with stenting. The intervention of interest is extended DAPT (beyond 12 months) compared with short-term DAPT (6–12 months). Studies will be selected for inclusion by two reviewers, and the quality will be assessed. The primary outcomes of interest are all-cause mortality and cardiovascular mortality. Secondary outcomes will be bleeding (major, minor and gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Outcomes will be assessed while on DAPT and after withdrawal of DAPT. Data will be summarised with respect to the number of included RCTs, number of participants, effect estimates and heterogeneity. Data will be reported separately based on patient demographics, procedural parameters (eg, stent types, lesion complexity and concurrent disease) and clinical presentation (eg, acute coronary syndromes, infarct type). Ethics and dissemination Our umbrella review aims to provide a comprehensive overview of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration and reimbursement of DAPT following PCI with stenting

  15. 一种新的免疫抑制剂FTY720对小鼠心脏移植的救治作用%FTY720, a new immunosuppressant,as rescue therapy in mouse cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    王铭辉; Vitaliy MILEKHIN; 张华; 黄洪铮

    2003-01-01

    AIM: FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induces long-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present study investigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouse heterotopic cardiac transplantation model. METHODS: BALB/c hearts were heterotopically grafted in C57BL/6 mice. FTY720, at the doses of 0.5, 1, and 5 mg@kg-1.d-1 or vehicle was administered to recipients once daily by oral gavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in the peripheral blood and the peripheral lymph nodes were determined on d 5 after transplantation. RESULTS: FTY720 prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed less lymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered the number of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesenteric lymph nodes and the peripheral lymph nodes. CONCLUSION: FTY720 used orally as rescue therapy significantly extended allograft survival in mouse heterotopic cardiac transplantation.

  16. Pre-procedural dual antiplatelet therapy in patients undergoing transcatheter aortic valve implantation increases risk of bleeding.

    Science.gov (United States)

    Hioki, Hirofumi; Watanabe, Yusuke; Kozuma, Ken; Nara, Yugo; Kawashima, Hideyuki; Kataoka, Akihisa; Yamamoto, Masanori; Takagi, Kensuke; Araki, Motoharu; Tada, Norio; Shirai, Shinichi; Yamanaka, Futoshi; Hayashida, Kentaro

    2017-03-01

    To evaluate the clinical benefit of pre-procedural antiplatelet therapy in patients undergoing transfemoral (TF) transcatheter aortic valve implantation (TAVI). OCEAN (Optimized transCathEter vAlvular interveNtion)-TAVI is a prospective, multicentre, observational cohort registry, enrolling 749 patients who underwent TAVI from October 2013 to August 2015 in Japan. We identified 540 patients (median age 85 years, 68.1% female) undergoing TF-TAVI; of these, 80 had no pre-procedural antiplatelet therapy and 460 had antiplatelet therapy. The endpoints were any bleeding (life-threatening, major, and minor bleeding) and thrombotic events (stroke, myocardial infarction, and valve thrombosis) during hospitalisation. Patients with dual antiplatelet therapy (DAPT) had a significantly higher incidence of any bleeding than those with single antiplatelet therapy (SAPT) (36.5% vs 27.5%, p=0.049) and no antiplatelet therapy (36.5% vs 21.3%, p=0.010). Patients without pre-procedural antiplatelet therapy did not experience an increased risk of thrombotic events. In multivariable logistic regression analysis, DAPT before TF-TAVI significantly increased any bleeding compared with SAPT (OR 2.05, 95% CI 1.16 to 3.65) and no antiplatelet therapy (OR 2.30, 95% CI 1.08 to 4.90). The current study demonstrated that DAPT before TF-TAVI increased the risk of bleeding compared with single or no antiplatelet therapy. Lower intensity antiplatelet therapy was not associated with thrombotic events. In modern practice, it might be reasonable to perform TAVI using single or no pre-procedural antiplatelet therapy with an expectation of no increase of adverse events. UMIN-ID; 000020423; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Determination of in vitro synergy for dual antimicrobial therapy against resistant Neisseria gonorrhoeae using Etest and agar dilution.

    Science.gov (United States)

    Wind, Carolien M; de Vries, Henry J C; van Dam, Alje P

    2015-03-01

    In response to antimicrobial resistance of Neisseria gonorrhoeae to last-resort extended-spectrum cephalosporins, combination therapy of azithromycin+ceftriaxone is now recommended. Dual therapy can be effective to treat monoresistant strains as well as multidrug-resistant strains, preferably employing the effect of in vitro synergy. As reports on in vitro synergy of azithromycin+ceftriaxone in N. gonorrhoeae are conflicting, in this study an evaluation of this combination was performed using a cross-wise Etest method and agar dilution. Synergy was defined as a fractional inhibitory concentration index (FICI) of ≤0.5. To identify other dual treatment options for gonorrhoea, in vitro synergy was evaluated for 65 dual antimicrobial combinations using Etest. Azithromycin, cefixime, ceftriaxone, colistin, ertapenem, fosfomycin, gentamicin, minocycline, moxifloxacin, rifampicin, spectinomycin and tigecycline were screened for synergy in all possible combinations. No synergy or antagonism was found for any of the 65 combinations. The geometric mean FICI ranged from 0.82 to 2.00. The mean FICI of azithromycin+ceftriaxone was 1.18 (Etest) and 0.55 (agar dilution). The difference between both methods did not result in a difference in interpretation of synergy. Ceftriaxone-resistant strain F89 was tested in all combinations and no synergy was found for any of them. Most importantly, the ceftriaxone minimum inhibitory concentration of F89 was not decreased below the breakpoint with any concentration of azithromycin.

  18. Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

    Science.gov (United States)

    Ke, Hengte; Yue, Xiuli; Wang, Jinrui; Xing, Sen; Zhang, Qian; Dai, Zhifei; Tian, Jie; Wang, Shumin; Jin, Yushen

    2014-03-26

    The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy.

  19. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    Science.gov (United States)

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  20. Dual Antiplatelet Therapy for 6 Months vs 12 Months After New-generation Drug-eluting Stent Implantation: Matched Analysis of ESTROFA-DAPT and ESTROFA-2.

    Science.gov (United States)

    de la Torre Hernández, José M; Oteo Domínguez, Juan F; Hernández, Felipe; García Camarero, Tamara; Abdul-Jawad Altisent, Omar; Rivero Crespo, Fernando; Cascón, José D; Zavala, Germán; Gimeno, Federico; Arrebola Moreno, Antonio L; Andraka, Leire; Gómez Menchero, Antonio; Bosa, Francisco; Carrillo, Xavier; Sánchez Recalde, Ángel; Alfonso, Fernando; Pérez de Prado, Armando; López Palop, Ramón; Sanchis, Juan; Diarte de Miguel, José A; Jiménez Navarro, Manuel; Muñoz, Luz; Ramírez Moreno, Antonio; Tizón Marcos, Helena

    2015-10-01

    The recommendation for dual antiplatelet therapy following drug-eluting stent implantation ranges from 6 months to 12 months or beyond. Recent trials have suggested the safety of a 6-month dual antiplatelet therapy regimen, yet certain caveats to these studies limit the applicability of this shorter duration dual antiplatelet therapy strategy in real world settings. A registry was constructed with consecutive recruitment of patients undergoing new-generation drug-eluting stent implantation and prescribed 6 months of dual antiplatelet therapy. Propensity score matching was undertaken with a historical cohort of patients treated with second-generation drug-eluting stents who received 12 months of dual antiplatelet therapy from the ESTROFA-2 registry. The sample size was calculated using a noninferiority basis and the primary endpoint was the combination of cardiac death, myocardial infarction, revascularization, or major bleeding at 12 months. The analysis included 1286 patients in each group, with no significant differences in baseline characteristics. The primary endpoint occurred in 5.0% and 6.6% in the 6-month and 12-month groups, respectively (P = .001 for noninferiority). The incidence of definite or probable stent thrombosis was 0.5% and 0.7% in the 6-month and 12-month groups, respectively (P = .4). Major bleeding events were lower in the 6-month group than in the 12-month group (0.8% vs 1.4%; P = .2) CONCLUSIONS: In selected patients in this large multicenter study, the safety and efficacy of a 6-month dual antiplatelet therapy regimen after implantation of new-generation drug-eluting stents appeared to be noninferior to those of a 12-month dual antiplatelet therapy regimen. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  1. Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes.

    Science.gov (United States)

    Alfredsson, Joakim; Neely, Benjamin; Neely, Megan L; Bhatt, Deepak L; Goodman, Shaun G; Tricoci, Pierluigi; Mahaffey, Kenneth W; Cornel, Jan H; White, Harvey D; Fox, Keith Aa; Prabhakaran, Dorairaj; Winters, Kenneth J; Armstrong, Paul W; Ohman, E Magnus; Roe, Matthew T

    2017-08-01

    Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patient's bleeding risk during DAPT treatment in the post-ACS setting. To develop a longitudinal bleeding risk prediction model, we analy sed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revasculari sation and treated with DAPT for a median of 14.8 months. We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomi sation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomi sation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneau's C-indices: 0.78 (SE = 0.024) for the GUSTO model and 0.67 (SE = 0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform risk -benefit considerations regarding the duration of DAPT following

  2. Incidence of pocket hematoma after electrophysiological device placement:dual antiplatelet therapy versus low-molecular-weight heparin regimen

    Institute of Scientific and Technical Information of China (English)

    Yan CHEN; Xin-Cun YANG; Kang MENG; Yun-Tao LI; Ming-Dong GAO; Ze-Chun ZENG; Jin-Rong ZHANG; Hong-Liang CONG; Yin LIU; Ru ZHAO; Le-Feng WANG

    2014-01-01

    Background Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49%vs. 16.47%, respectively;X2 = 6.66,P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012-0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket

  3. Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis.

    Science.gov (United States)

    Wong, Ka Sing Lawrence; Wang, Yilong; Leng, Xinyi; Mao, Chen; Tang, Jinling; Bath, Philip M W; Markus, Hugh S; Gorelick, Philip B; Liu, Liping; Lin, Wenhua; Wang, Yongjun

    2013-10-08

    Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA. We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60-0.80; Pstroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63-0.81; Pacute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world.

  4. Acoustic characterization of multi-element, dual-frequency transducers for high-intensity contact ultrasound therapy

    Science.gov (United States)

    Burtnyk, M.; N'Djin, W. A.; Persaud, L.; Bronskill, M.; Chopra, R.

    2012-10-01

    High-intensity contact ultrasound therapy can generate precise volumes of thermal damage in deep-seated tissue using interstitial or intracavitary devices. Multi-element, dual-frequency transducers offer increased spatial control of the heating pattern by enabling modulation of ultrasound power and frequency along the device. The performance and acoustic coupling between elements of simple, multi-element, dual-frequency transducers was measured. Transducer arrays were fabricated by cutting halfway through a rectangular plate of PZT, creating individual 4 × 5 mm segments with fundamental frequency (4.1 MHz) and third harmonic (13.3 MHz). Coupling between elements was investigated using a scanning laser vibrometer to measure transducer surface displacements at each frequency and different acoustic powers (0, 10, 20 W/cm2). The measured acoustic power was proportional to the input electrical power with no hysteresis and efficiencies >50% at both frequencies. Maximum transducer surface displacements were observed near element centers, reducing to ˜1/3-maximum near edges. The power and frequency of neighboring transducer segments had little impact on an element's output. In the worst case, an element operating at 4.1 MHz and 20 W/cm2 coupled only 1.5 W/cm2 to its immediate neighboring element. Multi-element, dual-frequency transducers were successfully constructed using a simple dicing method. Coupling between elements was minor, therefore the power and frequency of each transducer element could be considered independent.

  5. Liposome-like nanocapsules of dual drug-tailed betaine for cancer therapy.

    Science.gov (United States)

    Fang, Shuo; Niu, Yuge; Zhang, Wei; Zhang, Yemin; Yu, Liangli; Zhang, Yingyi; Li, Xinsong

    2015-09-30

    A novel dual drug-tailed betaine conjugate amphiphile has been firstly synthesized in which the polar headgroup is derived from glycine betaine and the hydrophobic tails are chlorambucil molecules. The newly prepared conjugate undergoes self-assembly to form stable liposome-like nanocapsules as an effective carrier with high drug loading capacity. The nanocapsules showed higher cytotoxic effects to cancer cell lines than those of free chlorambucil in vitro, and inhibited tumor growth effectively in vivo. This strategy that utilizes new dual drug-tailed betaine conjugate amphiphile to construct a self-assembled nanoparticle drug delivery system may have great potential in cancer chemotherapy.

  6. Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer

    Science.gov (United States)

    Park, Dongjin; Ahn, Kyung-Ohk; Jeong, Kyung-Chae; Choi, Yongdoo

    2016-05-01

    Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC.

  7. Diffuse Alveolar Hemorrhage Associated With Low Molecular Weight Heparin and Dual Anti-platelet Therapy After Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yildirim, Fatma; Kara, İskender; Okuyan, Hızır; Abaci, Adnan; Turkoglu, Melda; Aygencel, Gülbin

    2016-01-19

    A 54-year-old man had undergone to percutaneous coronary intervention (PCI) and two stents were placed to left anterior coronary artery and circumflex artery. Low molecular weight heparin (LMWH) together with ticagrelor 90 mg twice a day and acetylsalicylic acid (Aspirin) were started after PCI due to high risk of stent trombosis. On the fourth day of patient's follow-up in the intensive care unit (ICU), bloody secretion was started from endotracheal tube. Hemoglobin dropping, bilateral infiltration on the chest X-ray and bleeding from lung were diagnosed as diffuse alveolar hemorrhage (DAH). Apart from LMWH and antiplatelet therapies with aspirin and ticagrelor, there were no other identified risk factors for DAH. As far as we know, our report is the first case of DAH caused by LMWH and dual anti-platelet therapy including ticagrelor. This article is protected by copyright. All rights reserved.

  8. Gastroscopy-related adverse cardiac events and bleeding complications among patients treated with coronary stents and dual antiplatelet therapy

    DEFF Research Database (Denmark)

    Egholm, Gro; Thim, Troels; Madsen, Morten

    2016-01-01

    BACKGROUND AND STUDY AIMS: Dual antiplatelet therapy (DAPT) is recommended following percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DAPT is a risk factor for gastrointestinal bleeding. We aimed to quantify (1) the rate of gastroscopy within 12 months after PCI, (2) the rate...... of adverse cardiac events and gastroscopy-related bleeding complications within 30 days of gastroscopy, and (3) the association between antiplatelet therapy and these events. PATIENTS AND METHODS: Patients receiving gastroscopy within 12 months of PCI were identified and two nested case-control analyses were...... performed within the PCI cohort by linking Danish medical registries. Cases were patients with adverse cardiac events (cardiac death, myocardial infarction, or stent thrombosis) or hemostatic intervention. In both studies, controls were patients with gastroscopy including biopsy without adverse cardiac...

  9. Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats.

    Science.gov (United States)

    Sharma, Ashish Kumar; Kanawat, Devendra Singh; Mishra, Akanksha; Dhakad, Prashant Kumar; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi

    2014-12-01

    The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system. © The Author(s) 2013.

  10. Two-year retrospective economic evaluation of three dual-controller therapies used in the treatment of asthma.

    Science.gov (United States)

    O'Connor, Richard D; O'Donnell, John C; Pinto, Lionel A; Wiener, Douglas J; Legorreta, Antonio P

    2002-04-01

    To compare asthma-related health-care utilization and expenditures for patients prescribed one of three dual-controller therapies: fluticasone plus salmeterol, inhaled corticosteroids (ICS) [excluding fluticasone] plus salmeterol, and ICS plus a leukotriene modifier (LTM). Asthma-related medical claims from two major health plans were obtained for the 12 months before and after the initiation of dual therapy. A total of 1,325 patients > or = 12 years old with no claims for COPD or respiratory tract cancer were selected from the approximately 3.5 million lives covered. Multivariable regression was used to assess differences in asthma-related expenditures. To compensate for positive skew, all cost variables were log-transformed. Risk-adjusted total asthma-related costs for the fluticasone-plus-salmeterol cohort (n = 121), the ICS-plus-salmeterol cohort (n = 844), and the ICS-plus-LTM cohort (n = 360) [corrected] were $975, $1,089, and $1,268, respectively. Risk-adjusted pharmacy costs were $813, $841, and $996, respectively. Generalized linear modeling, controlling for baseline covariates, indicated that compared to ICS-plus-LTM therapy, fluticasone-plus-salmeterol therapy was associated with a significant reduction in asthma-related total (p = 0.0014) and pharmacy (p = 0.001) costs. Similar results were found when the ICS-plus-salmeterol group and the ICS-plus-LTM group were compared (p = 0.0001). The number of inpatient, outpatient, and emergency department visits and their corresponding costs were lower for the fluticasone-plus-salmeterol cohort, but were not statistically significant (p > 0.05). Results from managed-care practice suggest that treatment with fluticasone plus salmeterol, and more broadly ICS plus salmeterol, yield important cost savings when compared to treatment with ICS plus LTM.

  11. Immunosuppressive Therapy-Related Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  12. Immunosuppressive therapy for primary biliary cirrhosis

    NARCIS (Netherlands)

    R. Beukers (Rudolf)

    1992-01-01

    textabstractLack of knowledge about the specific cause and pathogenesis of PBC and its chronic and unpredictable course make it difficult to conduct and evaluate therapeutic studies. Moreover, it is hard to predict which patient will develop progressive disease and therefore is most likely to benefi

  13. Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hünemohr, Nora, E-mail: n.huenemohr@dkfz.de; Greilich, Steffen [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg (Germany); Paganetti, Harald; Seco, Joao [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Jäkel, Oliver [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg, Germany and Department of Radiation Oncology and Radiation Therapy, University Hospital of Heidelberg, 69120 Heidelberg (Germany)

    2014-06-15

    Purpose: The authors describe a novel method of predicting mass density and elemental mass fractions of tissues from dual energy CT (DECT) data for Monte Carlo (MC) based dose planning. Methods: The relative electron density ϱ{sub e} and effective atomic number Z{sub eff} are calculated for 71 tabulated tissue compositions. For MC simulations, the mass density is derived via one linear fit in the ϱ{sub e} that covers the entire range of tissue compositions (except lung tissue). Elemental mass fractions are predicted from the ϱ{sub e} and the Z{sub eff} in combination. Since particle therapy dose planning and verification is especially sensitive to accurate material assignment, differences to the ground truth are further analyzed for mass density, I-value predictions, and stopping power ratios (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12 tissues which showed the largest differences of single energy CT (SECT) to DECT are presented with respect to range uncertainties. The standard approach (SECT) and the new DECT approach are compared to reference Bragg peak positions. Results: Mean deviations to ground truth in mass density predictions could be reduced for soft tissue from (0.5±0.6)% (SECT) to (0.2±0.2)% with the DECT method. Maximum SPR deviations could be reduced significantly for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. MeanI-value deviations could be reduced for soft tissue from (1.1±1.4%, SECT) to (0.4±0.3%) with the presented method. Predictions of elemental composition were improved for every element. Mean and maximum deviations from ground truth of all elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. Dose studies showed that most of the 12 selected tissues would

  14. Effect of Water Immersion on Dual-task Performance: Implications for Aquatic Therapy.

    Science.gov (United States)

    Schaefer, Sydney Y; Louder, Talin J; Foster, Shayla; Bressel, Eadric

    2016-09-01

    Much is known about cardiovascular and biomechanical responses to exercise during water immersion, yet an understanding of the higher-order neural responses to water immersion is unclear. The purpose of this study was to compare cognitive and motor performance between land and water environments using a dual-task paradigm, which served as an indirect measure of cortical processing. A quasi-experimental crossover research design is used. Twenty-two healthy participants (age = 24.3 ± 5.24 years) and a single-case patient (age = 73) with mild cognitive impairment performed a cognitive (auditory vigilance) and motor (standing balance) task separately (single-task condition) and simultaneously (dual-task condition) on land and in chest-deep water. Listening errors from the auditory vigilance task and centre of pressure (CoP) area for the balance task measured cognitive and motor performance, respectively. Listening errors for the single-task and dual-task conditions were 42% and 45% lower for the water than land condition, respectively (effect size [ES] = 0.38 and 0.55). CoP area for the single-task and dual-task conditions, however, were 115% and 164% lower on land than in water, respectively, and were lower (≈8-33%) when balancing concurrently with the auditory vigilance task compared with balancing alone, regardless of environment (ES = 0.23-1.7). This trend was consistent for the single-case patient. Participants tended to make fewer 'cognitive' errors while immersed chest-deep in water than on land. These same participants also tended to display less postural sway under dual-task conditions, but more in water than on land. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Acometimento pulmonar na doença de Behçet: uma boa experiência com o uso de imunossupressores Pulmonary involvement in Behcet's disease: a positive single-center experience with the use of immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Alfredo Nicodemos Cruz Santana

    2008-06-01

    well as the survival, of patients with BD-related pulmonary involvement. METHODS: A retrospective review of our experience with pulmonary manifestations in patients with BD treated at our institution between January 1, 1988 and April 30, 2006. The clinical, radiological, treatment and survival data were obtained from medical charts. RESULTS: We identified 9 patients with BD-related pulmonary involvement. The mean age was 34 ± 11.5 years, and 7 of the patients were male. The radiological findings were as follows: pulmonary artery aneurysm (PAA in 8 patients; pulmonary embolism in 3 (translating to an incidence of 5.11 cases/100 patient-years; alveolar hemorrhage in one; and pulmonary hypertension in one. The treatment consisted of immunosuppression with prednisone plus chlorambucil (or cyclophosphamide or mycophenolate mofetil in all patients, with partial or complete resolution of the PAAs. One patient with a PAA and pulmonary hypertension also received sildenafil and warfarin, with good clinical and tomographic response (the first report in the English literature. In our sample, the mean duration of the follow-up period was 6.52 years. The three-year survival rate was 88.8%, as was the five-year survival rate. CONCLUSIONS: Patients with BD-related pulmonary involvement can present good survival with immunosuppressive therapy, and BD should be borne in mind as a possible cause of pulmonary hypertension and alveolar hemorrhage.

  16. Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy

    Science.gov (United States)

    Zhao, Xu; Yang, Cheng-Xiong; Chen, Li-Gong; Yan, Xiu-Ping

    2017-05-01

    The integrated functions of diagnostics and therapeutics make theranostics great potential for personalized medicine. Stimulus-responsive therapy allows spatial control of therapeutic effect only in the site of interest, and offers promising opportunities for imaging-guided precision therapy. However, the imaging strategies in previous stimulus-responsive therapies are `always on' or irreversible `turn on' modality, resulting in poor signal-to-noise ratios or even `false positive' results. Here we show the design of dual-stimuli-responsive and reversibly activatable nanoprobe for precision tumour-targeting and fluorescence-guided photothermal therapy. We fabricate the nanoprobe from asymmetric cyanine and glycosyl-functionalized gold nanorods (AuNRs) with matrix metalloproteinases (MMPs)-specific peptide as a linker to achieve MMPs/pH synergistic and pH reversible activation. The unique activation and glycosyl targetibility makes the nanoprobe bright only in tumour sites with negligible background, while AuNRs and asymmetric cyanine give synergistic photothermal effect. This work paves the way to designing efficient nanoprobes for precision theranostics.

  17. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Holland, G.N.; O' Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-06-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

  18. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  19. Immunosuppression in the elderly renal allograft recipient

    DEFF Research Database (Denmark)

    Montero, Nuria; Pérez-Sáez, María José; Pascual, Julio

    2016-01-01

    avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2...... receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account...... the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. CONCLUSIONS: There is very limited evidence for the benefits and harms...

  20. Heart transplant survival in non-human primates : T cell-directed immunosuppressive therapy and regulatory T cells for promotion of heart transplant survival in non-human primates

    NARCIS (Netherlands)

    E.M. Dons (Eefje)

    2013-01-01

    textabstractHeart transplantation significantly enhances the life expectancy of adult patients suffering heart failure, and infants born with malformations of their heart. However, there are many hurdles such as rejection of the transplanted organ, or side effects of the immunosuppressive drugs, tha

  1. Manganese Oxide-Coated Carbon Nanotubes As Dual-Modality Lymph Mapping Agents for Photothermal Therapy of Tumor Metastasis.

    Science.gov (United States)

    Wang, Sheng; Zhang, Qin; Yang, Peng; Yu, Xiangrong; Huang, Li-Yong; Shen, Shun; Cai, Sanjun

    2016-02-17

    Lymph node (LN) status is a major indicator of stage and survival of lung cancer patients. LN dissection is a primary option for lung cancer LN metastasis; however, this strategy elicits adverse effects and great trauma. Therefore, developing a minimally invasive technique to cure LN metastasis of lung cancer is desired. In this study, multiwalled carbon nanotubes (MWNTs) coated with manganese oxide (MnO) and polyethylene glycol (PEG) (namely MWNTs-MnO-PEG) was employed as a lymphatic theranostic agent to diagnose and treat metastatic LNs. After single local injection and lymph drainage were performed, regional LNs were clearly mapped by T1-weighted magnetic resonance (MR) of MnO and dark dye imaging of MWNTs. Meanwhile, metastatic LNs could be simultaneously ablated by near-infrared (NIR) irradiation under the guidance of dual-modality mapping. The excellent result was obtained in mice bearing LNs metastasis models, showing that MWNTs-MnO-PEG as a multifunctional theranostic agent was competent for dual-modality mapping guided photothermal therapy of metastatic LNs.

  2. Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

    Science.gov (United States)

    Sambola, Antonia; Montoro, J Bruno; Del Blanco, Bruno García; Llavero, Nadia; Barrabés, José A; Alfonso, Fernando; Bueno, Héctor; Cequier, Angel; Serra, Antonio; Zueco, Javier; Sabaté, Manel; Rodríguez-Leor, Oriol; García-Dorado, David

    2013-10-01

    Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications. © 2013.

  3. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem,1 Moonjeong Choi,1 Jiafu Cao,1 Yujeong Lee,1 Muhammad Ikram,2 Sik Yoon,2 Jaewon Lee,1 Hyung Ryong Moon,1 Min-Soo Kim,1 Yunjin Jung,1 Jin-Wook Yoo11College of Pharmacy, Pusan National University, Busan, 2Pusan National University School of Medicine, Yangsan, South KoreaAbstract: Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs, single time-dependent NPs (Time_NPs, and dual pH/time-dependent NPs (pH/Time_NPs were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy.Keywords: colon-specific delivery, dual-sensitive delivery

  4. Prevalence and Predictors of Early Discontinuation of Dual-Antiplatelet Therapy After Drug-Eluting Stent Implantation in Korean Population.

    Science.gov (United States)

    Cho, Mi Hee; Shin, Dong Wook; Yun, Jae Moon; Shin, Joong Hyun; Lee, Seung Pyo; Lee, Hyejin; Lim, Yoo Kyoung; Kim, Eun Ha; Kim, Hyun Kyoung

    2016-11-15

    The administration of antiplatelet drugs for months after a drug-eluting stent implantation is critical in decreasing the risk of complications, and premature discontinuation of antiplatelet therapy before the recommended period is the most important predictor for late complications. Therefore, we investigated the prevalence and associated factors of premature discontinuation of antiplatelet therapy in patients in Korea. This retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort data. Patients who were treated with dual-antiplatelet therapy (DAPT) were identified with medication prescription data. The Kaplan-Meier failure time plot was used to illustrate the cumulative probability of treatment discontinuation. Cox regression analysis was conducted to compare predictors of early discontinuation of DAPT. The characteristics of the early discontinuation group were not significantly different from the guideline concordance group, except for a higher prevalence of disability and a lower rate of chronic kidney disease. In a Cox regression model, the presence of hypertension was identified as a negative predictor of early discontinuation, and disability was not a statistically significant predictor. The prevalence of early discontinuation was 31.0% and seems to be significantly higher than those reported from prospective studies, which may more accurately reflect the real-world situation. In conclusion, physicians should make more effort to educate patients on the risk associated with premature discontinuation of antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent, and further studies investigating the reasons for nonadherence of DAPT are needed to improve DAPT compliance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Immunization of immunosuppressed patients with pneumococcal polysaccharide vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Ammann, A.J.; Schiffman, G.; Addiego, J.E.; Wara, W.M.; Wara, D.W.

    The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects. Nevertheless, absolute values were in the range that would be expected to result in protection. The duration of antibody response was not evaluated. Patients with carcinoma of the head and neck did not demonstrate a significant increase in antibody levels after vaccination, which was done at the time of radiation therapy. Two years after immunization antibody levels were lower with recovery at three years. However, these changes were not statistically significant. Decreased levels of antibody to pneumococcal polysaccharide types not present in the vaccine were observed. Studies of patients with carcinoma of the heat and neck demonstrated that radiation therapy has a profound immunosuppressive effect on antibody levels. More selective immunosuppressive therapy and/or an increase in the immunogenicity of the polysaccharides in the vaccine are required for protection of patients with malignancy.

  6. Dual-drug loaded nanoformulation with a galactosamine homing moiety for liver-targeted anticancer therapy.

    Science.gov (United States)

    Muhammad, Nafees; Wang, Xiaoyong; Wang, Kun; Zhu, Chengcheng; Zhu, Zhenzhu; Jiao, Yang; Guo, Zijian

    2016-08-16

    Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), Pt(IV) prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The Pt(IV) prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.

  7. Immunosuppressive drugs modulate the replication of hepatitis B virus (HBV in a hydrodynamic injection mouse model.

    Directory of Open Access Journals (Sweden)

    Junzhong Wang

    Full Text Available Hepatitis B virus (HBV reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.

  8. NO, Immunosuppression and Tumor Immmunotherapy

    OpenAIRE

    Hegardt, Pontus

    2002-01-01

    This study aims at clarifying the role of NO in the immunosuppression induced by in vivo tumor growth and by tumor immunotherapy, and determining whether the inhibition of NO production can be used as an adjuvant in tumor immunotherapy. We have shown previously that tumor cells, glioma (N32) and colon carcinoma (H1D2), when genetically engineered to express such immune stimulatory cytokines as IFN-g and IL-18, induce strong anti-tumor immune response, in immunized tumor-free rats, whereas onl...

  9. A rational approach to single, dual and triple therapy in COPD.

    Science.gov (United States)

    Calverley, Peter; Vlies, Ben

    2016-05-01

    The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well-being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence.

  10. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient].

    Science.gov (United States)

    Riveiro-Barciela, Mar; Buti, María

    2015-01-01

    Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  11. Immunosuppressive drugs for the treatment of autoimmune pancreatitis.

    Science.gov (United States)

    Pezzilli, Raffaele

    2014-01-01

    Autoimmune pancreatitis is one of the few diseases of the pancreas characterized by the possibility of curing the illness using immunosuppressant drugs. In this paper, the therapeutic approach used to treat autoimmune pancreatitis patients and the clinical outcome related to each treatment modality were reviewed. Steroids are useful in alleviating the symptoms of the acute presentation of autoimmune pancreatitis, but some questions remain open, such as a shared definition of the disease's remission as well as autoimmune pancreatitis relapse, the dosage of steroids in the symptomatic phase of the disease and the duration of steroid therapy. Finally, it should be determined if other immunosuppressive nonsteroidal drugs could become first-line therapy in patients with autoimmune pancreatitis without jaundice and without atrophic pancreas.

  12. Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

    Science.gov (United States)

    Chan, Lai Yue; Craik, David J.; Daly, Norelle L.

    2016-01-01

    Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers. PMID:27734947

  13. Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy.

    Science.gov (United States)

    Chan, Lai Yue; Craik, David J; Daly, Norelle L

    2016-10-13

    Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers.

  14. Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy.

    Science.gov (United States)

    Hsu, Kuan-Hui; Carbia, Blanca E; Plummer, Caryn; Chauhan, Anuj

    2015-08-01

    Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucoma with increased bioavailability and improved compliance. Contact lenses are developed for extended simultaneous release of timolol and dorzolamide, both of which are commonly prescribed hydrophilic drugs. The extended release is achieved by loading lenses with vitamin E barriers. In vitro release studies are performed with control and vitamin E loaded lenses for both drugs loaded separately and then together in the same lens. The safety and efficacy of combination therapy by contacts are demonstrated in a Beagle model of glaucoma. Simultaneous loading of timolol and dorzolamide increases the release duration of both drugs. Also vitamin E incorporation is highly effective in increasing the release durations of both drugs to about 2-days. The lenses loaded with both drugs exhibited superior IOP reduction compared to eye drops with about 6-fold lower drug loading. More importantly, combination therapy by continuous wear of vitamin E loaded contact for 2-days, followed by a new set of contacts for another two days, reduced IOP during the 4days of wear time and for another 8days after removal of the contacts. Vitamin E loading is very effective for providing combination therapy by contact lenses due to the increase in release durations of several drugs. The contact lens based therapy reduces IOP with lower drug dose compared to eye drops and may significantly improve the compliance as the effect of the therapy lasts significantly longer than the wear-duration.

  15. Dual antiplatelet therapy (clopidogrel and aspirin) is associated with increased all-cause mortality after carotid revascularization for asymptomatic carotid disease.

    Science.gov (United States)

    Alcocer, Francisco; Novak, Zdenek; Combs, Bart R; Lowman, Bruce; Passman, Marc A; Mujib, Marjan; Jordan, William D

    2014-04-01

    Despite the established guidelines, there is not a clear consensus about how to manage antiplatelet therapy after carotid surgery. It is a common practice in vascular surgery to use the combination of aspirin and clopidogrel in the treatment of such patients. In this work, we analyzed the impact on long-term survival of antiplatelet therapy in patients treated for carotid stenosis at a single institution over a 10-year period. Outcomes of 471 patients who underwent carotid intervention (1999-2008) were analyzed. Discharge prescription summaries were retrieved, and patients were divided into two groups according to their antiplatelet regimen: aspirin-only group and aspirin plus clopidogrel group. Only patients with a minimum of 30 days of confirmed antiplatelet therapy were included. All-cause mortality during follow-up represented the primary outcome, whereas stroke and bleeding at 30 days and during follow-up represented secondary end points. When local records were sparse, the Social Security Death Index was queried to confirm mortality. The International Classification of Diseases, 9th Revision (ICD-9 codes), was reviewed for treatment related to a bleeding condition. When divided by indication, there was an increased mortality rate in patients with asymptomatic carotid disease receiving dual antiplatelet therapy as compared with aspirin alone (47% vs 40%; P = .05). Patients with symptomatic carotid disease had a nonsignificant decrease in all-cause mortality if they received dual antiplatelet therapy (38% vs 39%; P = .53). In a subgroup analysis, there was a significant increase in the rate of all-cause mortality among patients older than 75 years receiving dual antiplatelet therapy for asymptomatic carotid disease (82% vs 56%; P = .001), whereas there was a nonsignificant decrease in mortality in patients older than 75 years receiving dual antiplatelet therapy for symptomatic carotid disease (47% vs 63%; P = .50). There was no difference in secondary outcomes

  16. One-week triple therapy with ranitidine bismuth citrate, clarithromycin and metronidazole versus two-week dual therapy with ranitidine bismuth citrate and clarithromycin for Helicobacter pylori infection : A randomized, clinical trial

    NARCIS (Netherlands)

    van der Wouden, EJ; Thijs, JC; van Zwet, AA; Kooy, A; Kleibeuker, JH

    1998-01-01

    Objective: The aim of this study was to compare the efficacy and side effects of l-wk triple therapy with ranitidine bismuth citrate (RBC) 400 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d., to 2-wk dual therapy with RBC 400 mg b.i.d. and clarithromycin 500 mg b.i.d. for H.

  17. Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

    Science.gov (United States)

    Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

    2017-03-01

    The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET

  18. Genetic factors for individual administration of immunosuppressants in organ transplantation

    Institute of Scientific and Technical Information of China (English)

    Song-Feng Yu; Li-Hua Wu; Shu-Sen Zheng

    2006-01-01

    BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug eflfux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conlficting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immuno-suppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

  19. Reduced Toxicity Breast Cancer Therapy: Changing the Or to And in Dual Targeted Therapeutics

    Science.gov (United States)

    2010-10-01

    targeted breast cancer therapeutics with the potentia l to dra matically improve speci ficity, reducing unwanted side effects . Here, we review our...of this work wa s to propose a new type of therapy activate d only in tumors presenting both a first AND second molecular target. Chemotherapy ...design (Figu re 1). With our light trigger system, we should be able to con trol th e position and the tim e of siRNA rele ase, lim iting any unwanted

  20. Prediction of infarction development after endovascular stroke therapy with dual-energy computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Djurdjevic, Tanja; Gizewski, Elke Ruth; Grams, Astrid Ellen [Medical University of Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Rehwald, Rafael; Glodny, Bernhard [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Knoflach, Michael; Matosevic, Benjamin; Kiechl, Stefan [Medical University of Innsbruck, Department of Neurology, Innsbruck (Austria)

    2017-03-15

    After intraarterial recanalisation (IAR), the haemorrhage and the blood-brain barrier (BBB) disruption can be distinguished using dual-energy computed tomography (DECT). The aim of the present study was to investigate whether future infarction development can be predicted from DECT. DECT scans of 20 patients showing 45 BBB disrupted areas after IAR were assessed and compared with follow-up examinations. Receiver operator characteristic (ROC) analyses using densities from the iodine map (IM) and virtual non-contrast (VNC) were performed. Future infarction areas are denser than future non-infarction areas on IM series (23.44 ± 24.86 vs. 5.77 ± 2.77; p < 0.0001) and more hypodense on VNC series (29.71 ± 3.33 vs. 35.33 ± 3.50; p < 0.0001). ROC analyses for the IM series showed an area under the curve (AUC) of 0.99 (cut-off: <9.97 HU; p < 0.05; sensitivity 91.18 %; specificity 100.00 %; accuracy 0.93) for the prediction of future infarctions. The AUC for the prediction of haemorrhagic infarctions was 0.78 (cut-off >17.13 HU; p < 0.05; sensitivity 90.00 %; specificity 62.86 %; accuracy 0.69). The VNC series allowed prediction of infarction volume. Future infarction development after IAR can be reliably predicted with the IM series. The prediction of haemorrhages and of infarction size is less reliable. (orig.)

  1. Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

    Science.gov (United States)

    Li, Jianbo; Zhang, Jinjie; Fu, Yao; Sun, Xun; Gong, Tao; Jiang, Jinghui; Zhang, Zhirong

    2015-08-28

    To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases.

  2. High near-infrared absorbing Cu5FeS4 nanoparticles for dual-modal imaging and photothermal therapy

    Science.gov (United States)

    Zhao, Qi; Yi, Xuan; Li, Meifang; Zhong, Xiaoyan; Shi, Quanliang; Yang, Kai

    2016-07-01

    Multifunctional nanomaterials have shown excellent and promising properties for cancer diagnosis and treatment. Herein, we have developed iron doped copper sulfide (Cu5FeS4) nanoparticles with a non-covalent polyethylene glycol (PEG) coating (Cu5FeS4-PEG) for tumor dual-modal imaging and photothermal therapy (PTT). The obtained Cu5FeS4-PEG nanoparticles with high near-infrared absorbance could be used for phototoacoustic (PA) imaging and PTT, whereas Fe3+ doping offer the nanoparticles the additional property for magnetic resonance (MR) imaging. As shown by PA imaging, Cu5FeS4-PEG exhibit a high tumor uptake (~10% ID g-1) after intravenous injection. In vitro and in vivo cancer treatment further confirm that Cu5FeS4-PEG could act as a novel therapeutic agent for PTT of cancer cells. Our study further promotes the potential applications of multifunctional nanomaterials in a range of tumor diagnoses and treatments.Multifunctional nanomaterials have shown excellent and promising properties for cancer diagnosis and treatment. Herein, we have developed iron doped copper sulfide (Cu5FeS4) nanoparticles with a non-covalent polyethylene glycol (PEG) coating (Cu5FeS4-PEG) for tumor dual-modal imaging and photothermal therapy (PTT). The obtained Cu5FeS4-PEG nanoparticles with high near-infrared absorbance could be used for phototoacoustic (PA) imaging and PTT, whereas Fe3+ doping offer the nanoparticles the additional property for magnetic resonance (MR) imaging. As shown by PA imaging, Cu5FeS4-PEG exhibit a high tumor uptake (~10% ID g-1) after intravenous injection. In vitro and in vivo cancer treatment further confirm that Cu5FeS4-PEG could act as a novel therapeutic agent for PTT of cancer cells. Our study further promotes the potential applications of multifunctional nanomaterials in a range of tumor diagnoses and treatments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr04444a

  3. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    Directory of Open Access Journals (Sweden)

    James A. Bourgeois

    2014-01-01

    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  4. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Oldgren, Jonas; Wallentin, Lars; Alexander, John H; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan

    2013-06-01

    Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

  5. Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy.

    Science.gov (United States)

    Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Driscoll-Shempp, Priscilla; Cutlip, Donald E; Steg, P Gabriel; Gershlick, Anthony H; Darius, Harald; Meredith, Ian T; Ormiston, John; Tanguay, Jean-François; Windecker, Stephan; Garratt, Kirk N; Kandzari, David E; Lee, David P; Simon, Daniel I; Iancu, Adrian Corneliu; Trebacz, Jaroslaw; Mauri, Laura

    2015-10-01

    This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS. Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES. Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months. Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p Antiplatelet Therapy Study [DAPT study]; NCT00977938). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    Science.gov (United States)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  7. Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres.

    Science.gov (United States)

    Li, Wei; Guo, Xiaomeng; Kong, Fenfen; Zhang, Hanbo; Luo, Lihua; Li, Qingpo; Zhu, Chunqi; Yang, Jie; Du, Yongzhong; You, Jian

    2017-07-28

    Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS). Our nanosystem (TNYL-ICG-HAuNS) was proved to possess significantly increased light stability, reactive oxygen species (ROS) production and photothermal effect under NIR light irradiation, thus presenting a remarkably enhanced antitumor efficacy. The up-regulation of nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) in cancer cells during PDT induced a significant increase of ABCG2, NQO-1 and HIF-1α expression, causing PDT resistance of the cells. Interestingly, ABCG2 expression could almost keep a normal level in the whole PDT process mediated by TNYL-ICG-HAuNS. After repeated irradiations, TNYL-ICG-HAuNS could still produce almost constant ROS in cells while the Nrf2 expression reduced significantly. Furthermore, PDT resistance induced an obvious decrease of the internalization of free ICG, but didn't influence the cell uptake of TNYL-ICG-HAuNS. Our data explained that TNYL-ICG-HAuNS could overcome the photodynamic resistance of cancer cells, acting as a promising modality for simultaneous photothermal and photodynamic cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. THE EFFECTIVENESS OF COMBINED THERAPY OF POSTMENOPAUSAL OSTEOPOROSIS WITH DUAL ACTION DRUGS

    Directory of Open Access Journals (Sweden)

    T. B. Minasov

    2011-01-01

    Full Text Available Osteoporosis is one of the most dangerous diseases occurred in elderly persons. Results of application of strontium ranelate in combination with calcium for treatment a women with a postmenopausal osteoporosis are resulted. The influence of this complex therapy on dynamics of mineral density indexes of a bone tissue and the level of bone metabolism were studied. Strontium ranelate both at monotherapy, and in combination with calcium promotes the augmentation of mineral density of bone tissue in an axial skeleton. The taking Strontium ranelate doesn’t cause serious side effect.

  9. A Dual-Beam Irradiation Facility for a Novel Hybrid Cancer Therapy

    CERN Document Server

    Sabchevski, Svilen; Ishiyama, Shintaro; Miyoshi, Norio; Tatsukawa, Toshiaki

    2012-01-01

    In this paper we present the main ideas and discuss both the feasibility and the conceptual design of a novel hybrid technique and equipment for an experimental cancer therapy based on the simultaneous and/or sequential application of two beams, namely a beam of neutrons and a CW (continuous wave) or intermittent sub-terahertz wave beam produced by a gyrotron for treatment of cancerous tumors. The main simulation tools for the development of the computer aided design (CAD) of the prospective experimental facility for clinical trials and study of such new medical technology are briefly reviewed. Some tasks for a further continuation of this feasibility analysis are formulated as well.

  10. Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy.

    Science.gov (United States)

    Kuo, Wen-Shuo; Chang, Yi-Ting; Cho, Keng-Chi; Chiu, Kuo-Chih; Lien, Chi-Hsiang; Yeh, Chen-Sheng; Chen, Shean-Jen

    2012-04-01

    Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) and gold nanoparticles (Au NPs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs and Au NPs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs and Au NPs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Moreover, the photochemical destruction ability would have a gradually increase depending on different sizes of Au NPs. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PTT and PDT proved to be efficiently killing cancer cells as compared to PTT or PDT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability. As a result, the preparation of Au-based nanomaterials conjugated with ICG as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  11. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

    2010-05-01

    The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy.

  12. Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Hagström, Marja V; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2015-04-01

    Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug.

  13. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Salgado Maria

    2011-12-01

    Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

  14. Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. A systematic review.

    Science.gov (United States)

    Vries, Minka J A; van der Meijden, Paola E J; Henskens, Yvonne M C; ten Cate-Hoek, Arina J; ten Cate, Hugo

    2016-01-01

    Patients with coronary artery disease are usually treated with dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Patients on DAPT are at risk of both ischaemic and bleeding events. Although side-lined for a long time, real-life studies have shown that both the incidence and the associated morbidity and mortality of out-of-hospital bleeding are high. This indicates that prevention of (post-interventional) bleeding is as important as prevention of ischaemia. For this purpose it is crucial to reliably identify patients with a high bleeding risk. In order to postulate an algorithm, which could help identifying these patients, we performed a systematic review to determine the value of previously proposed prognostic modalities for bleeding. We searched and appraised the following tools: platelet function tests, genetic tests, bleeding scores and questionnaires and haemostatic tests. Most studies indicated that low on-treatment platelet reactivity (LTPR), as measured by several platelet function tests, and the carriage of CYP2C19*17 allele were independent risk factors for bleeding. A bleeding score also proved to be helpful in identifying patients at risk. No studies on haemostatic tests were retrieved. Several patient characteristics were also identified as independent predictors of bleeding, such as older age, female sex and renal failure. Combining these risk factors we propose an algorithm that would hypothetically facilitate identification of those patients at highest risk, warranting prevention measures for bleeding. This could be a starting point for further research concerning the topic.

  15. Duration of dual antiplatelet therapy in patients treated with percutaneous coronary intervention for coronary chronic total occlusion.

    Science.gov (United States)

    Lee, Seung Hwa; Yang, Jeong Hoon; Choi, Seung-Hyuk; Park, Taek Kyu; Jang, Woo Jin; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Gwon, Hyeon-Cheol

    2017-01-01

    The duration of dual antiplatelet therapy (DAPT) after drug-eluting stent implantation in coronary chronic total occlusion (CTO) remains unclear. We retrospectively analyzed a total of 512 patients treated with percutaneous coronary intervention (PCI) in the Samsung Medical Center CTO registry. Patients were separated into ≤ 12-month (199, 38.9%) vs. > 12 month (313, 61.1%) based on DAPT duration with aspirin and clopidogrel. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE) during follow-up. Median follow-up duration was 67 (interquartile range: 51-84) months. MACCE occurred in 43 patients (21.6%) in the ≤ 12-month and 55 patients (17.6%) in the > 12-month groups. In the propensity-matched population, the rate of MACCE did not differ significantly between the ≤ 12-month and > 12-month group (19.4% vs. 18.8%; hazard ratio [HR], 0.95; 95% confidential interval [CI], 0.52-1.76, p = 0.88). Moreover, moderate or severe bleeding according to BARC criteria (type 2, 3 or 5) was also similar between the ≤ 12-month and > 12-month group (2.5% vs. 1.9%; HR, 1.00; 95% CI, 0.20-4.96, p = 0.99). Among patients treated with PCI for CTO, DAPT with durations of ≤ 12-month showed similar long-term clinical outcomes compared to > 12-month DAPT.

  16. Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy.

    Science.gov (United States)

    Chen, Ze; Zhao, Pengfei; Luo, Zhenyu; Zheng, Mingbin; Tian, Hao; Gong, Ping; Gao, Guanhui; Pan, Hong; Liu, Lanlan; Ma, Aiqing; Cui, Haodong; Ma, Yifan; Cai, Lintao

    2016-11-22

    An active cell membrane-camouflaged nanoparticle, owning to membrane antigens and membrane structure, can achieve special properties such as specific recognition, long blood circulation, and immune escaping. Herein, we reported a cancer cell membrane-cloaked nanoparticle system as a theranostic nanoplatform. The biomimetic nanoparticles (indocyanine green (ICG)-loaded and cancer cell membrane-coated nanoparticles, ICNPs) exhibit a core-shell nanostructure consisting of an ICG-polymeric core and cancer cell membrane shell. ICNPs demonstrated specific homologous targeting to cancer cells with good monodispersity, preferable photothermal response, and excellent fluorescence/photoacoustic (FL/PA) imaging properties. Benefited from the functionalization of the homologous binding adhesion molecules from cancer cell membranes, ICNPs significantly promoted cell endocytosis and homologous-targeting tumor accumulation in vivo. Moreover, ICNPs were also good at disguising as cells to decrease interception by the liver and kidney. Through near-infrared (NIR)-FL/PA dual-modal imaging, ICNPs could realize real-time monitored in vivo dynamic distribution with high spatial resolution and deep penetration. Under NIR laser irradiation, ICNPs exhibited highly efficient photothermal therapy to eradicate xenografted tumor. The robust ICNPs with homologous properties of cancer cell membranes can serve as a bionic nanoplatform for cancer-targeted imaging and phototherapy.

  17. Magnetic and fluorescent Gd2O3:Yb3+/Ln3+ nanoparticles for simultaneous upconversion luminescence/MR dual modal imaging and NIR-induced photodynamic therapy

    OpenAIRE

    LIU Jun; Huang, Long; Tian, Xiumei; Chen, Xiaoming; Shao, Yuanzhi; Xie, Fukang; Chen, Dihu; Li, Li

    2016-01-01

    The development of upconversion nanoparticles (UCNs) for theranostics application is a new strategy toward the accurate diagnosis and efficient treatment of cancer. Here, magnetic and fluorescent lanthanide-doped gadolinium oxide (Gd2O3) UCNs with bright upconversion luminescence (UCL) and high longitudinal relaxivity (r 1) are used for simultaneous magnetic resonance imaging (MRI)/UCL dual-modal imaging and photodynamic therapy (PDT). In vitro and in vivo MRI studies show that these products...

  18. Opportunistic Infections—Coming to the Limits of Immunosuppression?

    Science.gov (United States)

    Fishman, Jay A.

    2013-01-01

    Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients’ recent and distant epidemiological exposures and all factors that contribute to the patient’s net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future. PMID:24086067

  19. Opportunistic infections--coming to the limits of immunosuppression?

    Science.gov (United States)

    Fishman, Jay A

    2013-10-01

    Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients' recent and distant epidemiological exposures and all factors that contribute to the patient's net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future.

  20. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.

    Science.gov (United States)

    Hammer, Scott M; Vaida, Florin; Bennett, Kara K; Holohan, Mary K; Sheiner, Lewis; Eron, Joseph J; Wheat, Lawrence Joseph; Mitsuyasu, Ronald T; Gulick, Roy M; Valentine, Fred T; Aberg, Judith A; Rogers, Michael D; Karol, Cheryl N; Saah, Alfred J; Lewis, Ronald H; Bessen, Laura J; Brosgart, Carol; DeGruttola, Victor; Mellors, John W

    2002-07-10

    Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge. To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen. Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks. Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL. Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil. Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility. Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P =.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P<.001). Baseline HIV-1 hypersusceptibility to efavirenz (< or = 0.4-fold difference in susceptibility compared

  1. Docetaxel grafted magnetic nanoparticles as dual-therapeutic agentia for targeting perfusion therapy of urethral carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xiao; Wang, Zhen [Chongqing University, Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering (China); Dai, Hong [Chongqing Three Gorges Central Hospital, Department of Urology (China); Wang, Chunmei [Chongqing Three Gorges Central Hospital, Department of Orthopaedics (China); Xia, Bing [Guangzhou General Hospital of Guangzhou Military Command, Department of Medical Research (China); Chen, Lan; Pan, Jun, E-mail: panj@cqu.edu.cn [Chongqing University, Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering (China)

    2014-12-15

    Although urethral carcinoma has a low incidence, it suffers from a poor curative rate for the low retention of medicine around urethra. In the present study, we developed a kind of magnetic targeting perfusion chemotherapy to detain the chemotherapeutic drugs. Docetaxel (TXT) grafted magnetic nanoparticles, of which size was around 40 nm, were obtained by the conjugation of TXT to amino-functionalized iron oxide (NH{sub 2}@Fe{sub 3}O{sub 4}). They have shown great potential to be targeted to and stayed in desired position of urethra under the externally applied magnetism through in vitro mimic urethral study. Furthermore, they have validly inhibited the growth of direct-contacted human urethral squamous carcinoma cells in vitro (up to 56.34 %) by the combination effects of TXT and NH{sub 2}@Fe{sub 3}O{sub 4}, however, less than 3 % of TXT released from the nanoparticles, which was very few to impair the adjacent normal cells and tissues. Therefore, this kind of novel agentia was expected to hold great potential in clinic urethral carcinoma therapy.

  2. Evaluation of useful treatment which uses dual-energy when curing lung-cancer patient with stereotactic body radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyeong Jun; Lee, Yeong Gyu; Kim, Yeong Jae; Park, Yeong Gyu [Dept. of Radiation Oncology, Catholic University Seoul St Mary' s hospital, Seoul (Korea, Republic of)

    2016-12-15

    This study will evaluate the clinical utility by applying clinical schematic that uses monoenergy or dual energy as according to the location of tumors to the stereotactic radiotherapy to compare the change in actual dose given to the real tumor and the dose that locates adjacent to the tumor. CT images from a total of 10 patients were obtained and the clinical planning were planned based on the volumetric modulated arc therapy on monoenergy and dual energy. To analyze the change factor in the tumor, Conformity Index(CI) and Homogeneity Index(HI) and maximum dose quantity were each calculated and comparing the dose distribution on normal tissues, v{sub 10} and v{sub 5}, first ⁓ fourth ribs closest to the tumor (1st ⁓ 4th Rib), Spinal Cord, Esophagus and Trachea were selected. Also, in order to confirm the accuracy on which the planned dose distribution is really measured, the 2-dimensional ion chamber array was used to measure the dose distribution. As of the tumor factor, CI and HI showed a number close to 1 when the two energies were used. As of the maximum dose, the front chest wall showed 2% and the dorsal tumor showed equivalent value. As of normal tissue, the front chest wall tumors were reduced by 4%, 5% when both energies were used in the adjacent rib and as of trachea, reduced by 11%, 17%. As of the dose in the lung, as of v{sub 10}, it reduced by 1.5%, v{sub 5} by 1%. As of the rear chest wall, when both energies were used, the ribs adjacent to the tumors showed 6%, 1%, 4%, 12% reduction, and in the lung dose distribution, v{sub 10} reduced by 3%, and v{sub 5} reduced by 3.1%. The dose measurement in all energies were in accordance to the results of Gamma Index 3mm/3%. Conclusion : It is considered that rather than using monoenergy, utilizing double energy in the clinical setting can be more effectively applied to the superficial tumors.

  3. Diverticulitis in immunosuppressed patients: A fatal outcome requiring a new approach?

    Science.gov (United States)

    Brandl, Andreas; Kratzer, Theresa; Kafka-Ritsch, Reinhold; Braunwarth, Eva; Denecke, Christian; Weiss, Sascha; Atanasov, Georgi; Sucher, Robert; Biebl, Matthias; Aigner, Felix; Pratschke, Johann; Öllinger, Robert

    2016-01-01

    Background Diagnosis and treatment of diverticulitis in immunosuppressed patients are more challenging than in immunocompetent patients, as maintenance immunosuppressive therapies may mask symptoms or impair the patient’s ability to counteract the local and systemic infective sequelae of diverticulitis. The purpose of this study was to compare the in-hospital mortality and morbidity due to diverticulitis in immunosuppressed and immunocompetent patients and identify risk factors for lethal outcomes. Methods This retrospective study included consecutive in-patients who received treatment for colonic diverticulitis at our institution between April 2008 and April 2014. Patients were divided into immunocompetent and immunosuppressed groups. Primary end points were mortality and morbidity during treatment. Risk factors for death were evaluated. Results Of the 227 patients included, 15 (6.6%) were on immunosuppressive therapy for solid organ transplantation, autoimmune disease, or cerebral metastasis. Thirteen of them experienced colonic perforation and showed higher morbidity (p = 0.039). Immunosuppressed patients showed longer stays in hospital (27.6 v. 14.5 d, p = 0.016) and in the intensive care unit (9.8 v. 1.1 d, p operations (66% v. 29.2%, p = 0.004), and higher in-hospital mortality (20% v. 4.7%, p = 0.045). Age, perforated diverticulitis with diffuse peritonitis, emergency operation, C-reactive protein > 20 mg/dL, and immunosuppressive therapy were significant predictors of death. Age (hazard ratio [HR] 2.57, p = 0.008) and emergency operation (HR 3.03, p = 0.003) remained significant after multivariate analysis. Conclusion Morbidity and mortality due to sigmoid diverticulitis is significantly higher in immunosuppressed patients. Early diagnosis and treatment considering elective sigmoid resection for patients with former episodes of diverticulitis who are wait-listed for transplant is crucial to prevent death. PMID:27240131

  4. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy.

    Science.gov (United States)

    Casado Arroyo, Rubén; Polo-Tomas, Mónica; Roncalés, Maria P; Scheiman, James; Lanas, Angel

    2012-05-01

    Patients undergoing percutaneous coronary intervention require dual antiplatelet therapy. Proton-pump inhibitor (PPI) therapy is recommended for the prevention of upper GI complications. No study has determined the rate and type of GI bleeding events in such patients in routine clinical practice. Observational study with a prospective follow-up to confirm medication use and occurrence of events, which were validated. We have followed up a cohort of 1219 consecutive patients admitted for percutaneous coronary intervention in Zaragoza (Spain). Major GI bleeding and cardiovascular events. At discharge, 96.7% of patients were on dual antiplatelet therapy and 76.6% on PPI therapy, which increased up to 87.9% during follow-up of 2107.6 patient (pt) s-years (1.72±1.07 years/patient). There were eight patients who developed GI bleeding during hospitalisation and 27 patients during follow-up, (1.52 bleeds per 100 pt-years). Most GI bleeding events (81.4%) occurred during the first year (mean time to bleeding event: 7.03±7.65 months) and 84.6% of patients were on long-term PPI at the time of the bleed. Lower GI bleeding occurred more frequently than upper GI bleeding (74% lower vs. 26% upper). Peptic ulcer history and concomitant warfarin therapy were the only risk factors identified for upper or lower GI bleeding respectively. Among patients on dual antiplatelet therapy and PPI co-therapy, gastrointestinal bleeding episodes are more frequent in the lower GI tract. This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population.

  5. Immunosuppression and Chagas disease: a management challenge.

    Directory of Open Access Journals (Sweden)

    María-Jesús Pinazo

    Full Text Available Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been

  6. Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

    Energy Technology Data Exchange (ETDEWEB)

    Heumann, Thatcher R. [Emory University School of Medicine, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States); Parker, Sareeta [Department of Dermatology, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Biostatistics Shared Core Resource at WCI, Emory University, Atlanta, Georgia (United States); Dhabbaan, Anees [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States); Goodman, Michael [Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Lechowicz, Mary Jo; Flowers, Christopher R. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Department of Hematology and Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.

  7. Dual Antiplatelet Therapy Does Not Increase the Risk of Bleeding After Carotid Endarterectomy: Results of a Prospective Study.

    Science.gov (United States)

    Illuminati, Giulio; Schneider, Fabrice; Pizzardi, Giulia; Masci, Federica; Calio', Francesco G; Ricco, Jean-Baptiste

    2017-04-01

    The purpose of this study was to evaluate the risk of bleeding and other postoperative complications of carotid endarterectomy (CEA) in patients receiving dual antiplatelet therapy (DAPT). From January 2005 to December 2015, 188 consecutive patients undergoing CEA and receiving DAPT (aspirin 100 mg + clopidogrel 75 mg) were enrolled in a prospective study. All of them underwent coronary artery stenting with drug-eluting stents during the 6 months preceding CEA. In the entire series, DAPT was continued until the evening before CEA and resumed on the evening of the operation. All patients received intraoperative heparinization (5,000 IU before carotid clamping), which was reversed in 5 patients. In addition, all of them were given 2,000 units of enoxaparin every 12 hr after the operation, beginning 6 hr after completion of the operation, and until discharge. All the patients presented with carotid artery stenosis >70% (North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria), which was symptomatic in 42 patients (transient ischemic attack, n = 32; minor stroke, n = 10) and asymptomatic in 146. The CEA technique was standard, with prosthetic patch closure in 109 cases (58%) and eversion in 79 (42%). The primary endpoints of the study were occurrence of a postoperative cervical hematoma requiring surgical hemostasis and occurrence of cranial nerve injuries. The secondary endpoint was the combined rate of postoperative mortality, stroke, and myocardial ischemia. No postoperative cervical hematoma requiring surgical evacuation occurred in this series. One hypoglossal nerve palsy, regressive within 2 weeks, was observed. Postoperative mortality and neurologic and cardiac morbidity were nil. CEA under DAPT yields results comparable with those obtained in patients receiving a single antiplatelet treatment. No hemorrhagic complications were observed in this prospective series. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Duration of dual antiplatelet therapy after drug-eluting stent implantation: Meta-analysis of large randomised controlled trials

    Science.gov (United States)

    Tsoi, Man-Fung; Cheung, Ching-Lung; Cheung, Tommy Tsang; Wong, Ian Chi-Kei; Kumana, Cyrus Rustam; Tse, Hung-Fat; Cheung, Bernard Man-Yung

    2015-01-01

    Patients receive dual antiplatelet therapy (DAPT) for 6–12 months after drug-eluting stents (DES) implantation. The efficacy and safety of prolonged DAPT has been questioned. Therefore, we performed a meta-analysis on randomised trials comparing different DAPT durations. Literature was searched on trials comparing different DAPT durations. For inclusion, reports must report frequency of cardiovascular and bleeding events. Ten trials were included. Compared to 12 months, DAPT beyond 12 months was associated with fewer myocardial infarctions (OR 0.58 95%CI: 0.40–0.84) and stent thrombosis (OR 0.35 95%CI: 0.20–0.62), but more major bleeds (OR 1.60 95%CI: 1.22–2.11) and all-cause (OR 1.30 95%CI: 1.02–1.66) mortality. There was no significant alteration in risk of stroke (OR 0.93 95%CI: 0.66–1.31) or cardiac (OR 1.12 95%CI: 0.73–1.71) mortality. Compared to less than 12 months DAPT, 12 months DAPT did not reduce risk of myocardial infarction, stent thrombosis, strokes, cardiac or all-cause mortality, but increased the risk of major bleeds (OR 1.60 95%CI: 1.22–2.11). DAPT beyond 12 months reduce risk of myocardial infarction and stent thrombosis, but there is substantial increase in major bleeding risk and all-cause mortality which need to be addressed. DAPT beyond 12 months does not appear to alter the risk of stroke. PMID:26278959

  9. Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study.

    Science.gov (United States)

    Meredith, Ian T; Tanguay, Jean-François; Kereiakes, Dean J; Cutlip, Donald E; Yeh, Robert W; Garratt, Kirk N; Lee, David P; Steg, P Gabriel; Weaver, W Douglas; Holmes, David R; Brindis, Ralph G; Trebacz, Jaroslaw; Massaro, Joseph M; Hsieh, Wen-Hua; Mauri, Laura

    2016-05-03

    Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis. After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61). In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938. © 2016 American Heart Association, Inc.

  10. Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study

    Directory of Open Access Journals (Sweden)

    Pedro Cahn

    2014-11-01

    Full Text Available Introduction: Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. Materials and Methods: The GARDEL study compared the efficacy and safety of a dual therapy (DT combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. Results: Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT, triglycerides (142 mg/dL DT, 139 mg/Dl TT, LDL-C (94 mg/dL DT, 91 mg/dL TT and HDL-C (36 mg/dL DT, 35 mg/dL TT. Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL. Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT (Table 1. In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC. Conclusion: Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL-C in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction (1. So, the DT strategy, even missing the lipid-lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.

  11. Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV-patients. The BITER Study

    Directory of Open Access Journals (Sweden)

    Joaquín Portilla

    2014-11-01

    t observe any significant difference in lab parameters between baseline and week 24. Estimated glomerular filtrate rate increased from 83.4±24.7 to 88.5±56.8 mL/min, p=NS. Regarding reason to switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and non-applicable or unknown: 24 cases. Conclusions: Switching to dual therapy with DRV/r+ETR is an effective strategy in selected heavily experienced ART patients, even in those with LLV (<1000 cop/mL. This cART is safe and well tolerated, can reduce number of pills and improve adherence.

  12. A Rationale for Age-Adapted Immunosuppression in Organ Transplantation.

    Science.gov (United States)

    Krenzien, Felix; ElKhal, Abdallah; Quante, Markus; Rodriguez Cetina Biefer, Hector; Hirofumi, Uehara; Gabardi, Steven; Tullius, Stefan G

    2015-11-01

    Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants.Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors.This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

  13. Pneumonia in immunosuppressed patients; Pneumonien bei immunsupprimierten Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Solyanik, O.; Gaass, T.; Hellbach, K. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Dinkel, J. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Comprehensive Pneumology Center Munich (CPC-M), Muenchen (Germany)

    2017-01-15

    Pulmonary infections are a common complication in immunosuppressed patients with a frequently fatal prognosis despite modern prophylactic therapy. An early and correct diagnosis is important for initiation of the appropriate therapy. Chest radiography is the preferred initial imaging examination but is not accurate enough for the detection of pulmonary infections in immunosuppressed patients. Pneumonia is caused by a broad spectrum of pathogens in immunocompromised patients. In addition to imaging, the clinical history and epidemiology also play an important role in the diagnostics. Using epidemiological and anamnestic information, computed tomography (CT) shows a significantly better sensitivity and specificity particularly for the diagnosis of atypical forms of pneumonia. Due to the exact imaging of the different infiltration patterns CT provides an increased sensitivity with respect to the etiological classification of pulmonary infections. This article reviews in particular the radiological findings of commonly occurring pulmonary infections in immunosuppressed patients. (orig.) [German] Pneumonien bei immunsupprimierten Patienten sind haeufige Komplikationen, die trotzt moderner Prophylaxe toedlich verlaufen koennen. Eine korrekte Diagnose ist daher von entscheidender Bedeutung, um die richtige Therapie einleiten zu koennen. Die Roentgenthoraxaufnahme ist selten spezifisch genug fuer die genaue Einordnung atypischer Pneumonien in Folge einer Immunsuppression. Pneumonien unter Immunsuppression werden durch ein sehr breites Erregerspektrum verursacht. Eine wichtige Rolle bei der Diagnosefindung spielen neben der Bildgebung auch die klinische Anamnese und Epidemiologie. Mithilfe der klinischen Anamnese und Epidemiologie bietet die Computertomographie (CT) bei immunsupprimierten Patienten zum einen eine erhoehte Sensitivitaet bei der Detektion insbesondere atypischer Pneumonien. Zum anderen weist die CT durch die exakte Abbildung unterschiedlicher Infiltratmuster

  14. Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yoshinori, E-mail: yosakura@rri.kyoto-u.ac.jp; Tanaka, Hiroki; Kondo, Natsuko; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2015-11-15

    Purpose: Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a “dual phantom technique” for measuring the fast neutron component of dose is reported. Methods: One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % {sup 6}LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % {sup 6}LiOH solution based on the simulation results. Experimental characterization of the

  15. Cure of Helicobacter pylori-positive active duodenal ulcer patients: a double-blind, multicentre, 12-month study comparing a two-week dual vs a one-week triple therapy. GISU (Interdisciplinary Group for Ulcer Study).

    Science.gov (United States)

    Di Mario, F; Battaglia, F; Dal Bò, N; Leandro, G; Benedetti, E; Bottona, E; Caroli, A; Costan-Biedo, F; De Bastiani, R; Germanà, B; Andrea Grassi, S; Madia, D; Marcon, V; Marin, R; Monica, F; Olivieri, P; Orzes, N; Pilotto, A; Ronzani, G; Saggioro, A; Tafner, G

    2000-03-01

    To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection. A total of 165 patients with active duodenal ulcer were enrolled in the study. At entry, endoscopy, clinical examination and laboratory tests were performed. Histology and the rapid urease test were used to diagnose Helicobacter pylori infection. Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks (two-week, dual therapy) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week (one-week, triple therapy). Two and twelve months after cessation of therapy, endoscopy and clinical assessments were repeated. Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater (p<0.0001) in the triple therapy group (healing: 98.6%; Helicobacter pylori cure rate: 72.6%) than in the dual therapy group (healing: 77.3%; Helicobacter pylori cure rate: 33.3%). Ulcers healed more frequently in Helicobacter pyloricured than in Helicobacter pylori-not cured patients (94.9% vs. 77.2%; p<0.0022). After one year, Helicobacter pylori eradication was re-confirmed in 46/58 patients previously treated with the triple therapy and in 10/40 patients treated with the dual therapy [p<0.0001]. Only three duodenal ulcer relapses were observed throughout follow-up: all were in Helicobacter pylori-not cured patients. Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers. The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary. Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated.

  16. Multicenter evaluation of dual-therapy (omeprazol and amoxycillin) for Helicobacter pylori-associated duodenal and gastric ulcer (two years of the observation).

    Science.gov (United States)

    Gabryelewicz, A; Laszewicz, W; Dzieniszewski, J; Ciok, J; Marlicz, K; Bielecki, D; Popiela, T; Legutko, J; Knapik, Z; Poniewierka, E

    1997-09-01

    Treatment with the proton pump inhibitor (omeprazole) and single antibiotic (amoxycillin), two synergistic compounds, can cure Helicobacter pylori (H. pylori) infection, but this therapy is not as effective as had been expected. However, some studies show promising results. The aim of our study was to evaluate the effect of two weeks dual-therapy with omeprazole (O) and amoxycillin (A) on gastric (GU) and duodenal ulcer (DU) patients: ulcer healing, eradication of the H. pylori and recurrence rate of the ulcer. We studied 216 patients (aged 18-70) endoscopically proven GU (58 patients) and DU (158 patients). Rapid urease test from the two antrum biopses and two antral and two corporeal biopses using Giemsa stain method for confirmation of the H. pylori infection were used. The patients were treated with omeprazole 20 mg BID and amoxycillin 1.0 g BID for 2 weeks and investigated every 4 months during 2 years. Clearance effect of Hp infection was achieved in 65.1% GU and 66.4% DU patients. Eradication ("check point" after 4 months) in 43% DU and 56.6% GU patients was confirmed. Reinfection rate was found in 16% during 2 years. We conclude--dual-therapy (O and A) is not sufficiently effective to be recommended as an anti-H. pylori treatment. H. pylori eradication prevents recurrence of peptic ulcer and is an important issue in attempts to achieve permanent ulcer healing.

  17. Clinical Impact of Dual Antiplatelet Therapy Use in Patients Following Everolimus-eluting Stent Implantation: Insights from the SEEDS Study

    Directory of Open Access Journals (Sweden)

    Yao-Jun Zhang

    2015-01-01

    Full Text Available Background: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization at 2-year follow-up. Methods: The SEEDS study is a prospective, multicenter study, where patients (n = 1900 with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI, stroke, definite/probable stent thrombosis (ST, and major bleeding (Bleeding Academic Research Consortium II-V were investigated according to the DAPT status at 2-year follow-up. Results: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1% at 2 years follow-up, especially its components of all-cause death (0.9%, stroke (1.1%, and definite/probable ST (0.7%. DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715 and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968. Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%. There was a high frequency of major bleeding events (53/65, 82.5% occurred in patients receiving DAPT treatment. Conclusions: Prolonged DAPT use was not associated with improved clinical safety. The study

  18. [The incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding in patients taking dual antiplatelet therapy after percutaneous coronary intervention in south China].

    Science.gov (United States)

    Zhang, Z F; Sha, W H; Tan, G Y; Wang, Q Y

    2016-06-01

    To investigate the incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding (UGIB) in patients with acute coronary syndrome (ACS) who were administrated with aspirin and clopidogrel dual antiplatelet therapy after percutaneous coronary intervention (PCI). ACS patients who had undergone PCI in the cardiovascular institute of Guangdong General Hospital from September 2009 to August 2014 were retrospectively enrolled.The incidence of UGIB and clinical characteristics of ACS patients on dual antiplatelet therapy for 1 year after PCI were analyzed.Risk factors of UGIB were screened in the cohort of patients and sex and age matched controls with ratio 1∶3. A total of 9 118 ACS patients had undergone PCI and UGIB occurred in 189 patients (2.07%, 189/9 118) from September 2009 to August 2014. UGIB patients with history over one year, gastrointestinal tumors or varices or negative endoscopy were excluded.Thus the revised incidence of UGIB occurred was 0.61% in 56 patients (0.61%, 56/9 118) and appeared to decline year by year.Most patients (91.07%, 51/56) had melena or stool occult blood positive (OB+ ), while others had bloody stool or haematemesis.Most UGIB were ulcer-related which was proved by endoscopy, accounting for 67.86% (38/56). There were 24 cases with duodenal ulcer, 13 with gastric ulcer and 1 with complex ulcer, while others were gastric erosion, gastritis and duodenitis.The risk factors of UGIB were previous history of peptic ulcer (Pfactor (P0.05). PPI use for the prevention of UGIB after PCI didn't increase the recurrence of ACS. The incidence of UGIB is 0.61% in ACS patients on dual antiplatelet therapy (aspirin and clopidogrel) for 1 year after PCI and falls year by year.Administration of PPI after PCI protects patients from UGIB, especially in those with precious history of peptic ulcer and renal impairment.

  19. Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study.

    Science.gov (United States)

    Thierry, Antoine; Le Meur, Yannick; Ecotière, Laure; Abou-Ayache, Ramzi; Etienne, Isabelle; Laurent, Charlotte; Vuiblet, Vincent; Colosio, Charlotte; Bouvier, Nicolas; Aldigier, Jean-Claude; Rerolle, Jean-Philippe; Javaugue, Vincent; Gand, Elise; Bridoux, Frank; Essig, Marie; Hurault de Ligny, Bruno; Touchard, Guy

    2016-01-01

    Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654). © 2015 Steunstichting ESOT.

  20. Induction immunosuppression for lung transplantation with OKT3.

    Science.gov (United States)

    Wain, J C; Wright, C D; Ryan, D P; Zorb, S L; Mathisen, D J; Ginns, L C

    1999-01-01

    The use of OKT3, an anti-CD3 monoclonal antibody, for immunosuppressive therapy for lung transplantation has been restricted because of concerns regarding infectious risk and cardiopulmonary instability after its administration. Fifty-two patients received OKT3 (5 mg/d intravenously for 10 days) for induction of immunosuppressive therapy, along with azathioprine (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1) x d(-1)). Maintenance steroid therapy was begun on postoperative day 8. Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir was used in all patients. Serial transbronchial biopsy and measurements of pulmonary function were used to assess patients for evidence of infection or rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of cytomegalovirus antigenemia. The 30-day mortality rate was 4%; the in-hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The median length of intubation was 5 days, and the median hospital stay was 30 days. Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of arterial partial oxygen pressure to fraction of inspired oxygen showed no significant alteration after OKT3 dosage. Gram-negative pulmonary infections were identified in 12 patients. Aspergillus infection was seen in 7 patients. Cytomegalovirus infection in 8 patients responded to ganciclovir and did not affect mortality. Respiratory syncytial viral infection was seen in 7 patients. Acute rejection was never seen during OKT3 administration. No episodes of acute rejection were identified in 14 patients at any time postoperatively. In the remainder, episodes of acute rejection responded to steroid or antithymocyte globulin therapy. At a median length of follow-up of 31 months, freedom from obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after

  1. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    Science.gov (United States)

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection.

  2. Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Qin, Tao; Chen, Meng-Hua

    2015-10-09

    Since antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients is very important after intracoronary stenting, and because the most commonly used therapies have been the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel and the triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol, we aim to compare the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in T2DM patients. Systematic literature search was done from the databases of PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI) and WanFang. Randomized controlled trials (RCTs) comparing the effectiveness and safety between triple therapy and dual therapy in T2DM patients after coronary stents placement were included. Endpoints included major adverse cardiac effects (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), death, stent thrombosis, bleeding and adverse drug reactions during a 9-12 months period, as well as platelet activities. Four studies including 1005 patients reporting the adverse clinical outcomes and six studies including 519 patients reporting the platelet activities, with a total of 1524 patients have been analyzed in this meta-analysis. The pooling analysis shows that TAPT has significantly decreased the occurrence of MACEs (RR: 0.55; 95 % CI: 0.36-0.86, P = 0.009), TLR (RR 0.41; 95 % CI: 0.21-0.80, P = 0.008), TVR (RR 0.55; 95 % CI: 0.34-0.88, P = 0.01) and the overall incidence of Death/ Myocardial Infarction (MI)/TVR (RR 0.54; 95 % CI: 0.31-0.94, P = 0.03) during this 9 to 12 months follow up period after stents implantation. Stent thrombosis was almost similar in both groups. Bleeding seemed to favor DAPT but the result was not statistically significant. Platelet aggregation, platelet reactivity index (PRI) and platelet reactivity unit (PRU) were also reduced with Weight Mean Difference (WMD) of (-13.80; 95 % CI: -17

  3. 低剂量他克莫司为基础四联免疫抑制方案在肾移植中的应用:4年随访结果%Application of quadruple immunosuppressive therapies based on low-dosage Tacrolimus in kidney transplantation: 4-year follow-up results

    Institute of Scientific and Technical Information of China (English)

    黄赤兵; 许晓婷; 范明齐; 张艮甫; 王平贤; 冯嘉瑜; 肖亚

    2011-01-01

    BACKGROUND: There has been no consensus about selection and application dosage of immunosuppressive drugs after kidney transplantation due to great individual difference of drugs caused by gradual development and application. OBJECTIVE: To explore the immunosuppressive efficacy, the protective effects on renal function and the application safety of the quadruple immunosuppressive therapy based on low dosage of Tacrolimus (Tac) in kidney transplantation. METHODS: In the control group (schedule 11, Tac, mycophenolate mofetii (MMF), and prednisone were used. In the experimental group 1, reduced dose of Tac and MMF (schedule 2) and sirolimus (SRI.) were used. In the experimental group 2, reduced dose of Tac and MMF (schedule 2) and mizoribine (MZR) were used. The recipient lymphocyte reaction in each group was detected at 1,4 weeks, 6 months and 1 year after surgery. Urine transforming growth factor -β1 was tested once every 6 months. Liver and renal function, blood and urine routine, and blood glucose were examined every 13 months after kidney transplantation. All patients were followed up for 4 years.RESULTS AND CONCLUSION: There was no significant difference in acute rejection and infection rate among the three groups. At 4 weeks after transplantation, the recipient lymphocyte reaction was significantly weaker in the experimental groups 1, 2 than in the control group (P < 0.05). At 1 year after transplantation, transforming growth factor β1 concentration was significantly lower in the experimental groups 1, 2 than in the control group (P < 0.05). At 2 years after transplantation, serum creatinine and ciealimne clearance rate were significantly lower, and adverse events including liver damage and high glucose, were fewer in the experimental groups 1, 2 than in the control group (P<0.05). These findings suggest that compared with the triple immunosuppressive therapy based on conventional dose of Tac, the Quadruple immunosuppressive therapy shares the same

  4. Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

    Directory of Open Access Journals (Sweden)

    Dawkins Keith D

    2008-02-01

    Full Text Available Abstract Background To test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases. Methods From 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a short Thrombelastogram PlateletMapping™ (TEG and (b VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15 as previously described. Results There were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02 and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07. 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group. Conclusion This study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk.

  5. Taste-immunosuppression engram: reinforcement and extinction.

    Science.gov (United States)

    Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo

    2007-08-01

    Several Pavlovian conditioning paradigms have documented the brain's abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. Specifically, the naturalistic relation of food ingestion with its possible immune consequences facilitates taste-immune associations. Here we demonstrate that the saccharin taste can be associated with the immunosuppressive agent cyclosporine A, and that such taste-immune associative learning is subject to reinforcement. Furthermore, once consolidated, this saccharin-immunosuppression engram is resistant to extinction when avoidance behavior is assessed. More importantly, the more this engram is activated, either at association or extinction phases, the more pronounced is the conditioned immunosuppression.

  6. 68例儿童重型再生障碍性贫血强化免疫抑制治疗的疗效分析%Clinical Analysis of the Efficacy of Intensive Immunosuppressive Therapy in 68 Children With Severe Aplastic Anemia

    Institute of Scientific and Technical Information of China (English)

    陈纯; 李迎飞; 方建培; 薛红漫; 周敦华; 黄科; 徐宏贵; 郭海霞; 黄绍良

    2009-01-01

    IST亚组及其无反应IST亚组患儿治疗6个月后,有效率分别为76.9%(10/13)和45.6%(5/11),两亚组比较,差异有显著意义(P<0 05).G-CSF反应IST亚组患儿总有效率(92.3%,12 /13)较无反应IST亚组(54.5%,6/11)高,且差异有显著意义(P<0.05).结论 强化免疫抑制治疗重型再生障碍性贫血的疗效明显优于单用环孢菌素A. 强化免疫抑制治疗前,对粒细胞集落刺激因子有反应的患儿,强化免疫抑制治疗的预后相对较好.%children with severe aplastic anemia is better than that of cyclosporine A therapy only. Children with severe aplastic anemia who responded well to granulocyte colony stimulating factor had a better prognosis in the intensive immunosuppressive therapy.

  7. India ink incorporated multifunctional phase-transition nanodroplets for photoacoustic/ultrasound dual-modality imaging and photoacoustic effect based tumor therapy.

    Science.gov (United States)

    Jian, Jia; Liu, Chengbo; Gong, Yuping; Su, Lei; Zhang, Bin; Wang, Zhigang; Wang, Dong; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms-conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy.

  8. Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after immunosuppressive treatment.

    Science.gov (United States)

    Paola, Caramaschi; Giuliana, Festi; Giovanni, Orsolini; Cristian, Caimmi; Domenico, Biasi

    2016-07-01

    The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody.

  9. Conjugation of Vitamin E Analog α-TOS to Pt(IV) Complexes for Dual-Targeting Anticancer Therapy

    Science.gov (United States)

    Suntharalingam, Kogularamanan; Song, Ying

    2014-01-01

    We report two platinum(IV) complexes conjugated with a vitamin E analog, α-tocopherol succinate (α-TOS). One of the conjugates displays the activity of both cisplatin and αTOS in cancer cells, causing damage to DNA and mitochondria simultaneously. Accordingly, it serves as promising dual-targeting anticancer agent. PMID:24452361

  10. Vaccination against pox diseases under immunosuppressive conditions.

    Science.gov (United States)

    Mayr, A; Danner, K

    1978-01-01

    Pox diseases, caused either by smallpox virus or zoonotic pox viruses or animals, continue to be of potential danger to a non-vaccinated population. Mass vaccinations will become necessary and will then also be administered to persons with immunological aberrations. The vaccines which are presently used against smallpox cause severe complications in such hosts. In contrast, the attenuated vaccinia virus strain MVA is safe even under the conditions of immunosuppression and is recommended for the production of smallpox vaccines. Because of the special epizootic situations and the numerous immunosuppressive factors present in developing countries, the use of such a safe pox vaccine there is of crucial importance.

  11. Tuberculous pyomyositis in an immunosuppressed patient.

    Science.gov (United States)

    Osorio, Johanna; Barreto, Jackeline; Benavides, Jhonattan; López, Óscar; Cuenca, Ángela; García, Esperanza

    2016-02-23

    Tuberculous pyomyositis is a rare manifestation of extrapulmonary tuberculosis, most common in immunosuppressed patients, with clinical manifestations similar to pyomyositis of other etiologies, although with a lower age of presentation; notable risk factors include prior tuberculosis infection and pharmacological immunosuppression. Diagnosis depends on a high clinical suspicion of the infection in a susceptible population, given that microbiological isolation is often impossible. The response to treatment and prognosis are good. The case presented here is noteworthy given the rarity of this manifestation of tuberculosis and the slow response to first-line TB management in an HIV patient, despite susceptible microbiological isolation.

  12. Cutaneous toxoplasmosis in an immunosuppressed dog

    Directory of Open Access Journals (Sweden)

    T.S. Oliveira

    2014-06-01

    Full Text Available A seven-year-old female spayed Schnauzer was presented with cutaneous ulcerated nodular lesions shortly after the beginning of an immunosuppressive treatment for immune-mediated hemolytic disease. Cytology was performed and a great number of neutrophils and banana-shaped organisms were observed. Biopsy showed a neutrophilic and histiocytic dermatitis and panniculitis with myriads of intralesional bradyzoites cysts and tachyzoites. PCR analysis was positive for Toxoplasma gondii and negative for Neospora caninum. Immunohistochemistry confirmed intralesional T. gondii antigens. This study reports a rare case of cutaneous toxoplasmosis in an immunosuppressed dog.

  13. Developing New Immunosuppression for the Next Generation of Transplant Recipients: The Path Forward.

    Science.gov (United States)

    Stegall, M D; Morris, R E; Alloway, R R; Mannon, R B

    2016-04-01

    The development of new immunosuppressive drugs has slowed markedly over the past several years, and the outlook that improved therapy will be available to the next generation of transplant recipients is bleak. In this viewpoint, the authors outline some of important barriers to new drug development and suggest specific steps that the transplant community can take to overcome them.

  14. Factors that determine self-reported immunosuppressant adherence in kidney transplant recipients: a correlational study.

    Science.gov (United States)

    Weng, Li-Chueh; Yang, Ya-Chen; Huang, Hsiu-Li; Chiang, Yang-Jen; Tsai, Yu-Hsia

    2017-01-01

    To determine the factors related to immunosuppressant therapy adherence in kidney transplant recipients in Taiwan. Adherence to immunosuppressant treatment is critical after kidney transplantation. Thus, the factors associated with self-reported medication adherence in kidney transplant recipients warrant investigation. The study used a cross-sectional and correlation design. A convenience sample of 145 kidney transplant recipients was included. Structured questionnaires were used to collect data during 2012-2013. Multivariate linear regression was used to examine the factors related to immunosuppressant therapy adherence. Over half of the participants were female (54·5%), mean age was 45·5 years, and mean year after transplant was 7·4. The mean score for medication adherence was 29·73 (possible score range 7-35). The results of the multivariate linear regression analysis showed that gender (male), low income with a high school or college education, years after transplantation and concerns about medication taking were negatively associated with adherence. Medication self-efficacy was positively associated with adherence. Therapy-related factors, partnerships with healthcare professionals and having private healthcare insurance did not significantly relate to immunosuppressant therapy adherence. Kidney transplant recipients demonstrated a high level of adherence. Strategies to enhance patients' self-efficacy and alleviate concerns about medication may promote medication adherence. Male patients, those with a lower income and those with a higher education level, should be a focus of efforts to maintain adherence to the medication regimen. © 2016 John Wiley & Sons Ltd.

  15. Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy for treatment simplification: a multicenter analysis

    Directory of Open Access Journals (Sweden)

    Mauro Zaccarelli

    2014-11-01

    Full Text Available Background: To assess the role of drugs used in dual therapy (DT, as cART simplification, over the risk of treatment failure. Materials and Methods: Patients starting DT regimen composed by a boosted protease inhibitor (PI/r: darunavir (DRV/r, lopinavir (LPVr or atazanavir (ATV/r plus a second drug: raltegravir (RAL, maraviroc (MRV etravirine (ETR, lamivudine (3TC or tenofovir (TDF, this one generally used in HBV co-infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis. Results: Overall, 480 patients from six reference Italian centres were included: all switched to DT with HIV-RNA <500 cp/µL, 376 of them at <50 cp/µL. Patients who switched at <50 cp/µL showed a significant lower risk of treatment failure (13.3% versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005, thus the analysis was focused on this subgroup. Among the patients who switched at <50 cp/µL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%, ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r-RAL was the most widely used combination: 32.5%. Treatment failure was observed in 78 patients, of whom 38 virological and 35 for toxicity/intolerance, one patient died during follow-up and four patients interrupted for personal decision with undetectable HIV-RNA. At Cox Model, adjusted by gender, age, non-Italian origin, AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all the drugs had a positive effect on probability of failure (Figure, however the effect was significant for DRV/r (HR:0.21, 95% CI 0.07–0.59, p=0.03, ATV/r (0.30, 0.09–0.97, p=0.044 and RAL (0.37, 0.15–0.93, p=0.034; higher CD4 count at baseline was also associated with lower risk of failure while number of previous regimens with a higher risk. Moreover, ATV/r was found significant associated with significant higher risk of

  16. [Research advance on clinical blood transfusion and tumor therapy].

    Science.gov (United States)

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  17. Pancolitis with Ischemic Injury as a Complication of Immunosuppressive Treatment in a Patient with Autoimmune Hepatitis: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Dalbeni

    2012-01-01

    Full Text Available Ischemic colitis is a serious drug-induced adverse event. There are only few cases of immunosuppression-associated ischemic colitis described in the literature, but none with a pancolitis-like manifestation. We report the case of a 72-year-old female patient who developed a pancolitis with ischemic injury on immunosuppressive treatment with steroids and azathioprine for autoimmune hepatitis. The patient presented with massive rectal bleeding. Colonoscopy confirmed the diagnosis of pancolitis. The results of histological examination indicated drug-induced ischemic colitis involving the entire colon. This is the first case of ischemic pancolitis mimicking an inflammatory bowel disease (IBD in a patient with immunosuppressive therapy.

  18. Análise da eficácia do laser de baixa potência no tratamento da dor tendínea em ratos imunossuprimidos Analysis of low-level laser therapy efficacy on tendon pain treatment in immunosuppressed rats

    Directory of Open Access Journals (Sweden)

    Fernanda de Oliveira Busarello

    2011-12-01

    Full Text Available O comprometimento do sistema imune, que pode ser apresentado por indivíduos com doenças crônicas, leva à baixa resposta imunológica. Um dos tratamentos utilizados para lesões agudas em tendões é o laser de baixa potência, contudo há uma lacuna em relação ao seu uso em imunodepressão. O objetivo do presente estudo foi analisar se o laser de baixa potência é eficaz para o tratamento da dor em ratos imunodeprimidos submetidos a trauma tendíneo. Foram utilizados 23 ratos, machos, da linhagem Wistar, divididos aleatoriamente em três grupos: grupo controle, placebo e laser. Os animais foram imunodeprimidos (por administração de Ciclosporina A e submetidos à lesão no tendão calcâneo direito, com impacto de cerca de 0,40 J. Para o tratamento, utilizou-se laser de baixa potência, 670 nm, 30 mW e dose de 2 J/cm², durante 3 dias. A avaliação da dor foi realizada pelo teste de incapacidade funcional e por filamento de Von Frey digital. Os resultados apresentaram valores significativos para o grupo laser, com diminuição de dor funcional e da dor à pressão na superfície plantar e no local lesionado (tendão calcâneo direito. Portanto, concluiu-se que o laser de baixa potência é eficaz para reduzir a dor em ratos imunodeprimidos submetidos a trauma tendíneo.The commitment of immune system, which may be presented by individuals with chronic diseases, leading to a low immune response. One of the treatments used for acute injuries in tendons is the low-power laser, however there is a gap in relation to its use in immunosuppression. The objective of this study was to analyze if low-level laser therapy is effective for the treatment of pain in immunosuppressed rats subjected to trauma tendon. We used 23 male rats of Wistar strain, divided randomly in three groups: control group, placebo and laser. The animals were immunosuppressed (by administration of Cyclosporin A and underwent right Achilles tendon injury, with impact of about

  19. Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

    Science.gov (United States)

    Gatell Artigas, Josep María; Arribas López, José Ramón; Lázaro Y de Mercado, Pablo; Blasco Bravo, Antonio Javier

    2016-01-01

    The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. Decision tree models were built. probability of having viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials

    Science.gov (United States)

    Andreotti, Felicita; Schulze, Volker; Kołodziejczak, Michalina; Buffon, Antonino; Brouwer, Marc; Costa, Francesco; Kowalewski, Mariusz; Parati, Gianfranco; Lip, Gregory Y H; Kelm, Malte; Valgimigli, Marco

    2015-01-01

    Objective To assess the benefits and risks of short term (12 months) dual antiplatelet therapy (DAPT) versus standard 12 month therapy, following percutaneous coronary intervention with drug eluting stents. Design Meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library, and major congress proceedings, searched from 1 January 2002 to 16 February 2015. Review methods Trials comparing short term (12 months) DAPT regimens with standard 12 month duration of therapy. Primary outcomes were cardiovascular mortality, myocardial infarction, stent thrombosis, major bleeding, and all cause mortality. Results 10 randomised controlled trials (n=32 287) were included. Compared to 12 month DAPT, a short term course of therapy was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% confidence interval 0.36 to 0.92); P=0.02) with no significant differences in ischaemic or thrombotic outcomes. Extended versus 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (0.42 to 0.66); P12 months) could be considered. The increase in all cause but not cardiovascular death with extended DAPT requires further investigation. PMID:25883067

  1. Immunosuppressant therapy and bone loss in ligature-induced periodontitis: a study in rats Terapia imunossupressora e perda óssea em periodontite induzida por ligaduras: um estudo em ratos

    Directory of Open Access Journals (Sweden)

    Patricia Furtado Gonçalves

    2003-03-01

    Full Text Available Immunosuppressive agents have been recognized as a factor affecting the soft tissues of the periodontium. However, little is known about their effect on periodontitis progression. The aim of the present study was to investigate the influence of cyclosporin A (CsA administration, associated or not with nifedipine, on the bone loss resulting from a ligature-induced periodontitis in rats. Twenty-four adult male Wistar rats were used. After anesthesia, the mandibular first molar was randomly assigned to receive the cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments: Group A - saline solution; Group B - CsA (10 mg/kg; Group C - nifedipine (50 mg/kg; Group D - CsA (10 mg/kg plus nifedipine (50 mg/kg. Forty-five days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Intergroup analysis did not reveal significant differences regarding the bone loss volume in the ligated teeth between the experimental treatments (0.46 ± 0.11, 0.63 ± 0.32, 0.53 ± 0.14, 0.50 ± 0.18, for groups A, B, C and D, respectively - p > 0.05. However, intragroup analysis showed a greater bone loss volume in the ligated teeth than in the unligated ones (p O uso de agentes imunossupressores tem sido reconhecido como um fator que afeta os tecidos moles do periodonto. Entretanto, pouco se sabe sobre o seu efeito na progressão da periodontite. O objetivo do presente estudo foi investigar a influência da ciclosporina (CsA, associada ou não à nifedipina, na perda óssea resultante da periodontite induzida por ligaduras em ratos. Vinte e quatro ratos Wistar machos, adultos, foram incluídos no estudo. Após anestesia, foram colocadas ligaduras de fio de algodão ao redor do primeiro molar inferior direito ou esquerdo, aleatoriamente escolhido. O dente contralateral foi deixado sem ligadura. Os animais foram aleatoriamente

  2. Exploring risk factors of non-adherence to immunosuppressive medication in kidney transplant recipients : improving methodology & reorienting research goals

    OpenAIRE

    Denhaerynck, Kris

    2006-01-01

    8.1. Background and aim of the research program Non-adherence to the immunosuppressive therapy is an important issue in kidney transplant patients. About 20% of the kidney transplant patients are non-adherent to the immunosuppressive regimen. Non-adherence contributes to 20% of late acute rejection episodes and 16% of the graft losses, and results in a decreased number of quality adjusted life years. A strategy to increase long-term successful outcome after transplantation i...

  3. Merkel Cell Carcinoma in Immunosuppressed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Janice E. [Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States); Brewer, Jerry D., E-mail: brewer.jerry@mayo.edu [Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States)

    2014-06-27

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients.

  4. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    Science.gov (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  5. Evaluation of an immunosuppressant side effect instrument.

    Science.gov (United States)

    Winsett, Rebecca P; Arheart, Kris; Stratta, Robert J; Alloway, Rita; Wicks, Mona N; Gaber, A Osama; Hathaway, Donna K

    2004-09-01

    Clinicians continue to be compelled to evaluate the impact of immunosuppressive medication side effects on the quality of life of transplant recipients. We Were asked to develop an instrument to measure side effects in immunosuppressed transplant recipients. To construct an instrument that measures the impact and severity of side effects of immunosuppressive medications used in transplantation and to assess the reliability and validity of the newly developed instrument called the Memphis Survey. The instrument was constructed by a panel of physicians, nurses, and pharmacists with experience in treating transplant recipients. A small group of kidney transplant recipients (n= 13) provided pilot data for refining and testing the instrument. A national sample of kidney, liver, and heart transplant recipients (n = 505) provided data that were used to further develop the instrument. Factor analysis was used to determine the psychological dimensions underlying the instrument and to guide the construction of scales from the survey items. The instrument scales were then computed from the dataset of 505 transplant recipients to quantify the impact of immunosuppressant side effects on the quality of life of transplant recipients. Analyses showed the final instrument scales to be valid and reliable. Exploratory analysis suggests the need for further testing of the instrument to determine gender differences.

  6. Immunosuppressive Agents in the Treatment of Membranoproliferative Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Tülin AKAGÜN

    2011-05-01

    Full Text Available INTRODUCTION: Treatment of membranoproliferative glomerulonephritis (MPGN is often unrewarding with approximately 60% of patients progressing to end-stage renal failure within 10 years. In our study, we compared the efficacy of CS alone versus low dose CS + another immunosuppressive agent retrospectively. MATERIAL and METHODS: Twenty-nine patients (17 male with MPGN were retrospectively grouped according to treatment protocols with CS (methylprednisolone 1mg/kg (group 1, n=14; low dose CS + another immunosuppressive agent (group 2, n=15 [CS+MMF (n=6, CS+AZA (n=3, CS + CYC (n=6]. Patients in all groups also received renin-angiotensin system (RAS inhibitors. RESULTS: All patients received treatment for 12 months. Remission occurred in 12 patients (85.7% (9 complete and 3 partial in group 1 and 10 patients (66.6% (7 complete and 3 partial in group 2 (p=0.316. No patients required dialysis within the one year of follow up complications. At one year of treatment the baseline proteinuria levels of patients in group 1 (5.83+2.91 g/day and group 2 (5.37+4.05 g/day significantly decreased to 0.21+0.42 g/day (p=0.005 and 1.92+3.31 g/day (p=0.037, respectively. In the first year of treatment mean glomerular filtration rate (GFR values of patients in group 1 (105+40 mL/min was significantly higher than the group 2 (66+23 mL/min (p=0.005. CONCLUSION: There is no significant extra benefit in treating adult MPGN patients with combination therapy including low dose CS plus various immunosuppressive agents.

  7. Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

    Science.gov (United States)

    Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

    2016-03-01

    Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant. © The Author(s) 2015.

  8. Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy.

    Directory of Open Access Journals (Sweden)

    Eric K Hoobler

    Full Text Available We report the discovery of a novel dual inhibitor targeting fungal sterol 14α-demethylase (CYP51 or Erg11 and human 5-lipoxygenase (5-LOX with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC50 = 700 nM and CYP51 (IC50 = 43 nM in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 µM. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component.

  9. Betahistine plus piracetam dual therapy versus betahistine monotherapy for peripheral vestibular vertigo: a confounder-corrected subanalysis of the OSVaLD study.

    Science.gov (United States)

    Melnikov, Oleg A; Lilenko, Sergey V; Nauta, Jos; Ouwens, Mario J N M

    2015-11-01

    This subanalysis compared the efficacy of betahistine plus piracetam dual therapy versus betahistine monotherapy using data from OSVaLD, a 3 month, open-label, observational study conducted in 2272 patients with peripheral vestibular vertigo. Of the 1898 patients included in the original efficacy population, 1076 were from countries where betahistine plus piracetam dual therapy was prescribed to >1 patient; 114 of these 1076 patients (11%) received the dual therapy and 567 (53%) were treated with betahistine monotherapy; these patients were selected for analysis. Efficacy was assessed using the Dizziness Handicap Inventory (DHI) total and subscale scores. Propensity-score matching was used to correct potential differences in patient baseline characteristics between treatment groups. In addition, a subgroup analysis evaluated 103 patients treated with betahistine because of insufficient efficacy with their existing treatment. In the propensity-score matched, total-population evaluation, improvements in the DHI total and subscale scores were numerically greater in the betahistine plus piracetam group (n = 88) versus the betahistine group (n = 89) (DHI total, -42.9 vs. -37.6, respectively; DHI physical, -12.1 vs. -10.4; DHI emotional, -13.5 vs. -13.2) and statistically significant for the DHI functional score (-17.3 vs. -14.0, respectively, p = 0.01). The percentage of patients with no impairment at final visit was 27% with betahistine and 47% with betahistine plus piracetam; odds ratio: 2.3, 95% confidence interval: 1.3-2.4 (p = 0.007). Similar results were obtained in the subgroup analyses for patients whose current vertigo treatment was insufficient. The overall incidence of adverse events was low and similar in both groups, and there were no discontinuations due to drug-related adverse events. By using propensity-score matching, which controls for potential heterogeneity in patient baseline characteristics and small patient numbers, the results of this analysis

  10. Dual energy CT

    DEFF Research Database (Denmark)

    Al-Najami, Issam; Drue, Henrik Christian; Steele, Robert

    2017-01-01

    and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer. METHODS...... to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist. RESULTS: Changes in the quantitative parameters...

  11. Rapamycin/DiR loaded lipid-polyaniline nanoparticles for dual-modal imaging guided enhanced photothermal and antiangiogenic combination therapy.

    Science.gov (United States)

    Wang, Jinping; Guo, Fang; Yu, Meng; Liu, Li; Tan, Fengping; Yan, Ran; Li, Nan

    2016-09-10

    Imaging-guided photothermal therapy (PTT) has promising application for treating tumors. Nevertheless, so far imaging-guided photothermal drug-delivery systems have been developed with limited success for tumor chemo-photothermal therapy. In this study, as the proof-of-concept, a stimuli-responsive tumor-targeting rapamycin/DiR loaded lipid-polyaniline nanoparticle (RDLPNP) for dual-modal imaging-guided enhanced PTT efficacy is reported for the first time. In this system, polyaniline (PANI) with π-π electronic conjugated system and effective photothermal efficiency is chosen as the appropriate model receptor of fluorescence resonance energy transfer (FRET), and loaded cyanine probe (e.g., 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide, DiR) acts as the donor of near-infrared fluorescence (NIRF). In addition, rapamycin (RAPA), which is used as the antiangiogenesis chemotherapeutic drug, can cutdown the tumor vessels and delay tumor growth obviously. After intravenous treatment of RDLPNPs into Hela tumor bearing mice, fluorescent (from DiR) and enhanced photoacoustic (from DLPNPs) signals were found in tumor site over time, which reached to peak at the 6h time point. After irradiating with an NIR laser, a good anti-tumor effect was observed owing to the enhanced photothermal and antiangiogenic effect of RDLPNPs. These results show that the multifunctional nanoparticle can be used as a promising imaging-guided photothermal drug delivery nanoplatform for cancer therapy.

  12. Polydopamine-based coordination nanocomplex for T1/T2 dual mode magnetic resonance imaging-guided chemo-photothermal synergistic therapy.

    Science.gov (United States)

    Chen, Yan; Ai, Kelong; Liu, Jianhua; Ren, Xiaoyan; Jiang, Chunhuan; Lu, Lehui

    2016-01-01

    Despite the progress in the design and synthesis of theranostic agents, limitations on efficiency and safety offer significant room for improvement in these agents. Inspired by the natural binding ability of polydopamine nanospheres (PDAs) with iron ion, a simple and versatile synthesis strategy is developed to prepare biodegradable coordination polymer (CP) encapsulated PDAs nanocomplex (PDAs@CPx, x = 3, 6, 9). We found that the PDAs@CP3 can serve as a T1/T2 dual mode contrast agent (DMCA) for magnetic resonance imaging (MRI), which possesses high longitudinal (r1 = 7.524 mM(-1) s(-1)) and transverse (r2 = 45.92 mM(-1) s(-1)) relaxivities. In this system, benefitting from the high photothermal conversion efficiency derived from PDAs, DOX loaded PDAs@CP3 nanocomplex is able to not only destroy the tumor directly by heat, but also stimulate the chemotherapy by enabling NIR-responsive on demand delivery of DOX. To the best of our knowledge, this is the first example exploring the potential of PDAs@CPx nanocomplex for T1/T2 dual mode MRI-guided chemo-photothermal synergistic therapy. This work extends the currently available theranostic agents, and opens up new avenues to rationally design the high-performance T1/T2 DMCA.

  13. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

    Directory of Open Access Journals (Sweden)

    Gasparovic Hrvoje

    2012-08-01

    Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

  14. Curcumin–Piperine/Curcumin–Quercetin/Curcumin–Silibinin dual Drug-loaded Nanoparticulate Combination Therapy: A Novel Approach to Target and Treat Multidrug-resistant Cancers

    Directory of Open Access Journals (Sweden)

    C. Moorthi

    2013-01-01

    Full Text Available Curcumin is a functional food, which provides a wide range of health benefits including anti-cancer activity and considered as a suitable alternative for chemotherapeutic agents. However, cancer cells exhibit resistance to most chemotherapeutic agents including curcumin due to overexpression of adenosine triphosphate (ATP-binding cassette transporter proteins in the cancer cell membrane, which decrease the intracellular concentration of chemotherapeutic agents. Similarly, most chemotherapeutic agents including curcumin experience lack of cancer cell targeting, lack of aqueous solubility, rapid systemic clearance, intestinal metabolism and hepatic metabolism. These limitations hinder the clinical usefulness of curcumin in the treatment of multidrug-resistant cancers. In this article, we propose curcumin–piperine, or curcumin–quercetin or curcumin–silibinin dual drug-loaded nanoparticulate combination therapy to target and treat multidrug-resistant cancers. The proposed dual drug-loaded nanoparticulate combination is expected to reverse the multidrug resistance, prevent the rapid systemic clearance, prevent the intestinal and the hepatic metabolism, increase the aqueous solubility, enhance the bioavailability, target the cancer cells, produce a synergistic anti-cancer effect and enhance the efficacy of curcumin in the treatment of multidrug-resistant cancers.

  15. Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Natarajaswamy Kalleda

    2016-07-01

    Full Text Available Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.

  16. Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells.

    Science.gov (United States)

    Ruella, Marco; Klichinsky, Michael; Kenderian, Saad S; Shestova, Olga; Ziober, Amy; Kraft, Daniel O; Feldman, Michael; Wasik, Mariusz A; June, Carl H; Gill, Saar

    2017-10-01

    Patients with otherwise treatment-resistant Hodgkin lymphoma could benefit from chimeric antigen receptor T-cell (CART) therapy. However, Hodgkin lymphoma lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in Hodgkin lymphoma, CART should target both malignant cells and the TME. We demonstrated CD123 on both Hodgkin lymphoma cells and TME, including tumor-associated macrophages (TAM). In vitro, Hodgkin lymphoma cells convert macrophages toward immunosuppressive TAMs that inhibit T-cell proliferation. In contrast, anti-CD123 CART recognized and killed TAMs, thus overcoming immunosuppression. Finally, we showed in immunodeficient mouse models that CART123 eradicated Hodgkin lymphoma and established long-term immune memory. A novel platform that targets malignant cells and the microenvironment may be needed to successfully treat malignancies with an immunosuppressive milieu.Significance: Anti-CD123 chimeric antigen receptor T cells target both the malignant cells and TAMs in Hodgkin lymphoma, thereby eliminating an important immunosuppressive component of the tumor microenvironment. Cancer Discov; 7(10); 1154-67. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047. ©2017 American Association for Cancer Research.

  17. Immunosuppression enhances oncolytic adenovirus replication and antitumor efficacy in the Syrian hamster model.

    Science.gov (United States)

    Thomas, Maria A; Spencer, Jacqueline F; Toth, Karoly; Sagartz, John E; Phillips, Nancy J; Wold, William S M

    2008-10-01

    We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth.

  18. Clinical Trials for Immunosuppression in Transplantation; The Case for Reform and Change in Direction.

    Science.gov (United States)

    O'Connell, Philip J; Kuypers, Dirk; Mannon, Roslyn R; Abecassis, Michael; Chadban, Stephen; Gill, John S; Murphy, Barbara; Nickerson, Peter W; Schold, Jesse D; Stock, Peter; Seron, Daniel; Alloway, Rita; Bromberg, Jonathan; Budde, Klemens; Jordan, Stanley; Legendre, Christophe; Lefaucheur, Carmen; Sarwall, Minnie; Segev, Dorry; Stegall, Mark D; Tullius, Stefan G; Wong, Germaine; Woodle, E Steve; Ascher, Nancy; Morris, Randall E

    2017-02-15

    Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared to current standard of care. Current trial design is not leading to novel therapies improving long term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered. Issues that need to be addressed include but are not limited to: prevention of subclinical rejection in the first year, better 5 and 10 year graft outcomes, more effective treatment for high immunological risk and sensitized (including DSA) patients, immunosuppressive combinations that are better tolerated by patients with fewer side effects and less morbidity and mortality. In September 2015 the Transplantation Society convened a group of transplant clinical trial experts to address these problems. The aims were to substantially realign the priorities of clinical trials for renal transplant immunosuppression with the current unmet needs and to propose new designs for clinical trials for transplant immunosuppression. Moving forward, the transplant community needs to provide trial data that will identify superior treatment options for patient subgroups and allow new agents to be evaluated for efficacy and safety and achieve timely regulatory approval. Trial designs for new transplant immunosuppression must be intelligently restructured in order to ensure that short- and long-term clinical outcomes continue to improve.

  19. Plant Polyphenol-Assisted Green Synthesis of Hollow CoPt Alloy Nanoparticles for Dual-Modality Imaging Guided Photothermal Therapy.

    Science.gov (United States)

    Song, Xiao-Rong; Yu, Shu-Xian; Jin, Gui-Xiao; Wang, Xiaoyong; Chen, Jianzhong; Li, Juan; Liu, Gang; Yang, Huang-Hao

    2016-03-01

    Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA-NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size-controlled synthesis of HCPA-NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal-chelating ability of the polyphenols. Further studies show that HCPA-NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual-modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Europium-155 as a source for dual energy cone beam computed tomography in adaptive proton therapy: A simulation study.

    Science.gov (United States)

    Zhu, Jiahua; Penfold, Scott N

    2017-07-04

    To investigate the feasibility of a 3D imaging system utilizing a (155) Eu source and pixelated cadmium-zinc-telluride (CZT) detector for applications in adaptive radiotherapy. Specifically, to compare the reconstructed stopping power ratio (SPR) values of a head phantom obtained with the proposed imaging technique with theoretical SPR values. A Geant4 Monte Carlo simulation was performed with the novel imaging system. The simulation was repeated with a typical 120 kV X-ray tube spectrum while maintaining all other parameters. Dual energy (155) Eu source cone beam computed tomography (CBCT) images were reconstructed with an iterative projection algorithm known as total variation superiorization with diagonally relaxed orthogonal projections (TVS-DROP). Single energy 120 kV source CBCT images were also reconstructed with TVS-DROP. Reconstructed images were converted to SPR with stoichiometric calibration techniques based on ICRU 44 tissues. Quantitative accuracy of reconstructed attenuation coefficient images as well as SPR images were compared. Images generated by gamma emissions of (155) Eu showed superior contrast resolution to those generated by the 120 kV spectrum. Quantitatively, all reconstructed images correlated with reference attenuation coefficients of the head phantom within 1 standard deviation. Images generated with the (155) Eu source showed a smaller standard deviation of pixel values. Use of a dual energy conversion into SPR resulted in superior SPR accuracy with the (155) Eu source. (155) Eu was found to display desirable qualities when used as a source for dual energy CBCT. Further work is required to demonstrate whether the simulation results presented here can be translated into an experimental prototype. © 2017 American Association of Physicists in Medicine.

  1. Both positive mental health and psychopathology should be monitored in psychotherapy: Confirmation for the dual-factor model in acceptance and commitment therapy.

    Science.gov (United States)

    Trompetter, H R; Lamers, S M A; Westerhof, G J; Fledderus, M; Bohlmeijer, E T

    2017-04-01

    The dual-factor model of mental health suggests that enhancing positive mental health and alleviating psychopathology do not automatically go hand-in-hand. This study investigates the relationship between the effectiveness on depression/anxiety symptoms and positive mental health of Acceptance and Commitment Therapy (ACT). It draws on RCT data (n = 250) of a self-help ACT. Patients' depression/anxiety symptoms and positive mental health were completed at baseline, at post-intervention after nine weeks, and at follow-up after five months. Percentage of unique variance of depression/anxiety symptoms explained by positive mental health (and vice versa), and the degree of classificatory agreement between improvements in positive mental health and depression/anxiety, were examined using regression analysis and Reliable Change Index (RCI). Positive mental health, i.e. baseline and change, explained 15% and 12% of the variance in follow-up depression and anxiety symptoms, beyond the 7% and 9% that was explained by baseline levels of depression and anxiety. Depression and anxiety symptoms, i.e., baseline and change, explained 10% and 9% of the variance in follow-up positive mental health, on top of the 35% that was explained by baseline levels of positive mental health. Cross-classification of the Reliable Changes showed that 64% of the participants that improved during the ACT-intervention, improved on either depression symptoms or positive mental health, and 72% of the participants improved on either anxiety symptoms or positive mental health. The findings support the dual-factor model and suggest that it is important to systematically implement measures of both psychopathology and positive mental health in mental health care and therapy evaluations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Colonic diverticular hemorrhage associated with the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, antiplatelet drugs, and dual therapy.

    Science.gov (United States)

    Nagata, Naoyoshi; Niikura, Ryota; Aoki, Tomonori; Shimbo, Takuro; Kishida, Yoshihiro; Sekine, Katsunori; Tanaka, Shohei; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Akiyama, Junichi; Yanase, Mikio; Mizokami, Masashi; Uemura, Naomi

    2014-10-01

    The effects of various medications on lower gastrointestinal tract remains unknown. Here, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and antiplatelet drugs associated with diverticular bleeding. This prospective study involved patients with diverticulosis who underwent colonoscopy. Alcohol and smoking, medications, and Charlson comorbidity index and Gastrointestinal Symptom Rating Scale scores were assessed. The medications evaluated were nine kinds of NSAIDs, two kinds of low-dose aspirin, 10 kinds of nonaspirin antiplatelet drugs, three kinds of anticoagulants, acetaminophen, and corticosteroids. Adjusted odds ratios (aOR) were estimated by a logistic regression model. A total of 911 patients with non-bleeding diverticula (n = 758) and bleeding diverticula (n = 153) were enrolled. Independent risk factors were alcohol consumption (light drinker, aOR 3.4; ≥ moderate drinker, aOR 3.3), smoking index (≥ 400, aOR 2.0), NSAIDs (aOR 4.6), low-dose aspirin (aOR 1.9), and nonaspirin antiplatelet drugs (aOR 2.2). The drugs significantly associated with bleeding were loxoprofen (aOR 5.0), diclofenac (aOR 3.1), diclofenac suppository (aOR 8.0), etodolac (aOR 4.9), enteric-coated aspirin (aOR 3.9), buffered aspirin (aOR 9.9), clopidogrel (aOR 2.5), and cilostazol (aOR 7.3). Dual therapy carried a higher risk than monotherapy (single NSAID, aOR 3.6, P antiplatelet drug, aOR 2.0, P antiplatelet drugs are risk factors for diverticular bleeding. The magnitude of risk may differ between different kinds of NSAIDs and antiplatelet drugs, and dual therapy with NSAIDs or antiplatelet drugs increases the risk of bleeding. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Prospective Randomized Study of Sarpogrelate Versus Clopidogrel-based Dual Antiplatelet Therapies in Patients Undergoing Femoropopliteal Arterial Endovascular Interventions: Preliminary Results

    Institute of Scientific and Technical Information of China (English)

    Yue-Xin Chen; Wen-Da Wang; Xiao-Jun Song; Yong-Quan Gu; Hong-Yan Tian; He-Jie Hu; Ji-Chun Zhao

    2015-01-01

    Background:Sarpogrelate is a selective 5-hydroxytryptamine (5-HT) receptor subtype 2A antagonist which blocks 5-HT induced platelet aggregation and proliferation of vascular smooth muscle cells.We compared the efficacy of sarpogrelate-based dual antiplatelet therapies for the prevention of restenosis and target lesion revascularization (TLR) rates comparing with that of clopidogrel after percutaneous endovascular interventions (EVIs) of femoropopliteal (FP) arterial lesions.Methods:This prospective,multicenter,randomized clinical trial recruited a total of 120 patients with successful EVI of FP lesions at seven centers across China between January 2011 and June 2012.Patients were randomized to receive either sarpogrelate (1 00 mg trice daily for 6 months,n =63) or clopidogrel (75 mg once daily for 6 months,n =57).All patients also received oral aspirin (100 mg once daily for 12 months).Clinical follow-up was conducted up to 12 months postprocedure.Results:There was no significant difference between the two groups in basic demographic data.The restenosis rate was higher in the clopidogrel group (22.80%) than in sarpogrelate group (17.50%),but there was no significant difference between these two groups (P =0.465).The TLR rate,ipsilateral amputation rate,mortality in all-cause and bleeding rate were also similar in the two groups (P > 0.05).Conclusions:Aspirin plus sarpogrelate is a comparable antithrombotic regimen to aspirin plus clopidogrel after EVI of FP arterial lesions.Dual antiplatelet therapies might play an important role in preventing restenosis after successful EVI of FP lesions.

  4. Comparison of proton therapy treatment planning for head tumors with a pencil beam algorithm on dual and single energy CT images

    Energy Technology Data Exchange (ETDEWEB)

    Hudobivnik, Nace; Dedes, George; Parodi, Katia; Landry, Guillaume, E-mail: g.landry@lmu.de [Department of Medical Physics, Ludwig-Maximilians-University, Munich 85748 (Germany); Schwarz, Florian; Johnson, Thorsten; Sommer, Wieland H. [Institute for Clinical Radiology, Ludwig Maximilians University Hospital Munich, 81377 Munich (Germany); Agolli, Linda [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich 81377, Germany and Radiation Oncology, Sant’ Andrea Hospital, Sapienza University, Rome 00189 (Italy); Tessonnier, Thomas [Department of Medical Physics, Ludwig-Maximilians-University, Munich 85748, Germany and Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg (Germany); Verhaegen, Frank [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht 6229 ET, the Netherlands and Medical Physics Unit, Department of Oncology, McGill University, Montreal, Quebec H3A 0G4 (Canada); Thieke, Christian; Belka, Claus [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich 81377 (Germany)

    2016-01-15

    Purpose: Dual energy CT (DECT) has recently been proposed as an improvement over single energy CT (SECT) for stopping power ratio (SPR) estimation for proton therapy treatment planning (TP), thereby potentially reducing range uncertainties. Published literature investigated phantoms. This study aims at performing proton therapy TP on SECT and DECT head images of the same patients and at evaluating whether the reported improved DECT SPR accuracy translates into clinically relevant range shifts in clinical head treatment scenarios. Methods: Two phantoms were scanned at a last generation dual source DECT scanner at 90 and 150 kVp with Sn filtration. The first phantom (Gammex phantom) was used to calibrate the scanner in terms of SPR while the second served as evaluation (CIRS phantom). DECT images of five head trauma patients were used as surrogate cancer patient images for TP of proton therapy. Pencil beam algorithm based TP was performed on SECT and DECT images and the dose distributions corresponding to the optimized proton plans were calculated using a Monte Carlo (MC) simulation platform using the same patient geometry for both plans obtained from conversion of the 150 kVp images. Range shifts between the MC dose distributions from SECT and DECT plans were assessed using 2D range maps. Results: SPR root mean square errors (RMSEs) for the inserts of the Gammex phantom were 1.9%, 1.8%, and 1.2% for SECT phantom calibration (SECT{sub phantom}), SECT stoichiometric calibration (SECT{sub stoichiometric}), and DECT calibration, respectively. For the CIRS phantom, these were 3.6%, 1.6%, and 1.0%. When investigating patient anatomy, group median range differences of up to −1.4% were observed for head cases when comparing SECT{sub stoichiometric} with DECT. For this calibration the 25th and 75th percentiles varied from −2% to 0% across the five patients. The group median was found to be limited to 0.5% when using SECT{sub phantom} and the 25th and 75th percentiles

  5. Immunity and immunosuppression in experimental visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  6. Immunosuppressive lignans isolated from Saururus chinensis.

    Science.gov (United States)

    Park, Shin-Young; Lee, Sung Hak; Choi, Woo Hyuck; Koh, Eun Mi; Seo, Jee Hee; Ryu, Shi Yong; Kim, Young Sup; Kwon, Dae Young; Koh, Woo Suk

    2007-06-01

    Bioactivity-guided fractionation of Saururus chinensis (Saururaceae) using a lymphoproliferation assay led us to isolate 5 lignans (compounds 1 - 5). Compounds 1 - 5 were identified as sauchinone, (-)-saucerneol, saucerneol C, manassantin A, and manassantin B, respectively, by spectroscopic analyses. The immunosuppressive activities of the active compounds were evaluated using lymphoproliferation, mixed leukocyte response, and Th1/Th2 cytokine assays. The relative potency was in the order: manassantin A, B > (-)-saucerneol > saucerneol C > sauchinone.

  7. Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhou, Yijiang; Wang, Yanwei; Wu, Yutao; Huang, Chaoyang; Yan, Hui; Zhu, Weiguo; Xu, Weiwei; Zhang, Li; Zhu, Jianhua

    2017-06-15

    High on-treatment platelet reactivity (HPR) represents a strong risk factor for thrombotic events after PCI. We aim to evaluate the efficacy and safety of individualizing intensified dual antiplatelet therapy (DAPT) in PCI-treated patients with HPR based on platelet function testing (PFT). Electronic databases were searched for randomized control trials that reported the clinical outcomes of using an intensified antiplatelet protocol with P2Y12 receptor inhibitor comparing with standard maintenance dose of clopidogrel on the basis of platelet function testing. Clinical endpoints were assessed. From 2005 to 2016, thirteen clinical studies comprising 7290 patients were included for analysis. Compared with standard antiplatelet therapy with clopidogrel, the intensified protocol based on platelet function testing was associated with a significant reduction in major adverse cardiovascular events (RR:0.55, 95% CI: 0.36-0.84, p = 0.005), cardiovascular death (RR:0.60, 95% CI: 0.38-0.96, p = 0.03), stent thrombosis (RR:0.58, 95% CI: 0.36-0.93, p = 0.02) and target vessel revascularization (RR:0.33, 95% CI: 0.14-0.76, p = 0.009). No significant difference was found in the rate of bleeding events between intensified and standard protocol. Compared with standard clopidogrel therapy, individualized intensified antiplatelet therapy on the basis of platelet reactivity testing reduces the incidence of cardiovascular events in patient undergoing PCI, without increasing the risk of bleeding.

  8. Living related liver transplant following bone marrow transplantation from same donor: long-term survival without immunosuppression.

    Science.gov (United States)

    Granot, E; Loewenthal, R; Jakobovich, E; Gazit, E; Sokal, E; Reding, R

    2012-02-01

    We report long-term (seven yr) immunological tolerance in a 16-yr-old boy, to a liver allograft donated by his father following a bone marrow transplant at age 2.5 yr from the same donor. The bone marrow transplant was complicated by severe GVHD leading to liver failure and the ensuing need for a liver transplant, performed under planned avoidance of immunosuppression. At one wk post-transplant, although a liver biopsy was histologically compatible with acute rejection, favorable clinical and biochemical evolution precluded initiating immunosuppressive therapy, thus highlighting the need for caution when interpreting early histological changes so that administration of unnecessary immunosuppression can be avoided. Induction of tolerance in transplant recipients remains an elusive goal. In those patients who had received conventional bone marrow transplants and had endured the consequences of GVHD, development of macrochimerism may allow immunosuppression-free solid organ transplantation from the same donor.

  9. Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects of tacrolimus, cyclosporine, and prednisone.

    Science.gov (United States)

    Dall'Agnol, D J R; Hauschildt, A T; Lima, M B; Corá, L A; Teixeira, M C B; Américo, M F

    2014-01-01

    Triple immunosuppressive therapy after organ transplantation may cause several gastrointestinal disturbances. It is difficult to identify which drug causes more complications, requiring an appropriate animal model. The aim was to compare the gastrointestinal transit in immunosuppressed rats under triple immunosuppressive therapy. Male rats were immunosuppressed by gavage during 14 days with tacrolimus (n = 10), cyclosporine (n = 12), and prednisone (n = 9). Animals received a magnetic pellet before (control) and after treatment that was monitored at predetermined intervals by AC biosusceptometry, a noninvasive and radiation-free technique. The following parameters were measured: creatinine serum, mean time of gastric emptying (MGET), mean time to reach cecum (MCAT), and mean transit time through small bowel (MSBTT). The differences were analyzed by ANOVA (Tukey). Our results showed that MGET of animals treated with prednisone, cyclosporine, and tacrolimus were reduced compared with control subjects (P prednisone compared with control subjects (P prednisone and tacrolimus presented a reduced MGET (P < .05 and P < .01, respectively) compared with cyclosporine. Our data showed a low serum creatinine level and no difference among groups regarding renal function. In summary, cyclosporine has less effect on the gastrointestinal transit; however, all of these drugs should be carefully prescribed to prevent gastrointestinal symptoms and improve quality of life after transplantation.

  10. Dual Differentiation-Exogenous Mesenchymal Stem Cell Therapy for Traumatic Spinal Cord Injury Repair in a Murine Hemisection Model

    Directory of Open Access Journals (Sweden)

    Hai Liu

    2013-01-01

    Full Text Available Mesenchymal stem cell (MSC transplantation has shown tremendous promise as a therapy for repair of various tissues of the musculoskeletal, vascular, and central nervous systems. Based on this success, recent research in this field has focused on complex tissue damage, such as that which occurs from traumatic spinal cord injury (TSCI. As the critical event for successful exogenous, MSC therapy is their migration to the injury site, which allows for their anti-inflammatory and morphogenic effects on fracture healing, neuronal regeneration, and functional recover. Thus, there is a need for a cost-effective in vivo model that can faithfully recapitulate the salient features of the injury, therapy, and recovery. To address this, we review the recent advances in exogenous MSC therapy for TSCI and traumatic vertebral fracture repair and the existing challenges regarding their translational applications. We also describe a novel murine model designed to take advantage of multidisciplinary collaborations between musculoskeletal and neuroscience researchers, which is needed to establish an efficacious MSC therapy for TSCI.

  11. Varicella-zoster virus immunity in dermatological patients on systemic immunosuppressant treatment.

    LENUS (Irish Health Repository)

    Hackett, C B

    2012-02-01

    BACKGROUND: Primary varicella infection is caused by varicella-zoster virus (VZV). It is a common childhood infection, which is usually benign but can occasionally cause morbidity and mortality. In immunosuppressed adults, atypical presentation and disseminated disease can occur with significant morbidity and mortality. A VZV vaccine is available. OBJECTIVES: This study was designed to measure the prevalence of immunity to VZV and to determine the predictive value of a self-reported history of varicella infection in a population of dermatological patients receiving systemic immunosuppressant therapy. We sought to assess the need for routine serological testing for varicella-zoster immunity in this cohort. METHODS: Serological testing for VZV immunity was done on 228 patients receiving systemic immunosuppressive treatment for a dermatological condition. Information regarding a history of previous primary VZV infection was obtained from each patient. RESULTS: Two hundred and twenty-eight patients had VZV serology performed. The mean age of the patients was 49.6 years. The prevalence of VZV seropositivity in this cohort was 98.7%. One hundred and two patients (44.7%) reported having a definite history of primary VZV. The sensitivity of a self-reported history of VZV infection was 45.3% with a specificity of 100%. The positive and negative predictive values of a self-reported history of VZV for serologically confirmed immunity were 100% and 2.3%, respectively. CONCLUSIONS: The prevalence of VZV IgG antibodies in our cohort of Irish dermatology patients receiving immunosuppressive therapy is 98.7%. A recalled history of varicella infection is a good predictor of serological immunity. This study has shown that there are VZV-susceptible individuals within our cohort. These patients did not have a clear history of previous infection. We recommend serological testing of patients without a clear history of infection prior to the commencement of immunosuppressive therapy and

  12. Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

    2017-02-01

    Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

  13. Magnetic and fluorescent Gd2O3:Yb(3+)/Ln(3+) nanoparticles for simultaneous upconversion luminescence/MR dual modal imaging and NIR-induced photodynamic therapy.

    Science.gov (United States)

    Liu, Jun; Huang, Long; Tian, Xiumei; Chen, Xiaoming; Shao, Yuanzhi; Xie, Fukang; Chen, Dihu; Li, Li

    The development of upconversion nanoparticles (UCNs) for theranostics application is a new strategy toward the accurate diagnosis and efficient treatment of cancer. Here, magnetic and fluorescent lanthanide-doped gadolinium oxide (Gd2O3) UCNs with bright upconversion luminescence (UCL) and high longitudinal relaxivity (r1) are used for simultaneous magnetic resonance imaging (MRI)/UCL dual-modal imaging and photodynamic therapy (PDT). In vitro and in vivo MRI studies show that these products can serve as good MRI contrast agents. The bright upconversion luminescence of the products allows their use as fluorescence nanoprobes for live cells imaging. We also utilized the luminescence-emission capability of the UCNs for the activation of a photosensitizer to achieve significant PDT results. To the best of our knowledge, this study is the first use of lanthanide-doped Gd2O3 UCNs in a theranostics application. This investigation provides a useful platform for the development of Gd2O3-based UCNs for clinical diagnosis, treatment, and imaging-guided therapy of cancer.

  14. Magnetic and fluorescent Gd2O3:Yb3+/Ln3+ nanoparticles for simultaneous upconversion luminescence/MR dual modal imaging and NIR-induced photodynamic therapy

    Science.gov (United States)

    Liu, Jun; Huang, Long; Tian, Xiumei; Chen, Xiaoming; Shao, Yuanzhi; Xie, Fukang; Chen, Dihu; Li, Li

    2017-01-01

    The development of upconversion nanoparticles (UCNs) for theranostics application is a new strategy toward the accurate diagnosis and efficient treatment of cancer. Here, magnetic and fluorescent lanthanide-doped gadolinium oxide (Gd2O3) UCNs with bright upconversion luminescence (UCL) and high longitudinal relaxivity (r1) are used for simultaneous magnetic resonance imaging (MRI)/UCL dual-modal imaging and photodynamic therapy (PDT). In vitro and in vivo MRI studies show that these products can serve as good MRI contrast agents. The bright upconversion luminescence of the products allows their use as fluorescence nanoprobes for live cells imaging. We also utilized the luminescence-emission capability of the UCNs for the activation of a photosensitizer to achieve significant PDT results. To the best of our knowledge, this study is the first use of lanthanide-doped Gd2O3 UCNs in a theranostics application. This investigation provides a useful platform for the development of Gd2O3-based UCNs for clinical diagnosis, treatment, and imaging-guided therapy of cancer. PMID:28031709

  15. Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer

    Science.gov (United States)

    Yang, Lu; Cheng, Juan; Chen, Yuli; Yu, Shengjie; Liu, Fengqiu; Sun, Yang; Chen, Yu; Ran, Haitao

    2017-01-01

    Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both in vitro and in vivo. Additionally, the CNPs are capable of staining lymph nodes, which can contribute significantly to the identification of LNs with naked eyes. With increased laser energy, the CNPs exhibit the high performance in killing the breast cancer cells both in vitro and in vivo, due to the photothermal effect induced from the CNs within CNPs. These results suggest that the developed multifunctional phase-transition nanodroplets have high potential to act as the theranostic agents in both SLNs detection and therapy of metastatic LNs. PMID:28338071

  16. A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

    Science.gov (United States)

    Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

    2015-04-01

    This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Autoimmune Hepatitis-related Cirrhosis: Clinical Features and Effectiveness of Immunosuppressive Treatment in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Yan-Ni Li; Huan Ma; Lu Zhou; Jie Zhang; Li-Ping Guo; Shu-Qian Li; Yi-Qi Qian

    2016-01-01

    Background:The long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable.However,little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment.We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital.Methods:Patients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed.Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study.Among these patients,87 presented with cirrhosis when initially diagnosed for AIH.Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis.Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed.Independent risk factors were assessed for predicting the prognosis of patients.The t-test and Cox regression statistical analysis were used.Results:In total,96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy.The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients (84.4%),whereas 9/96 (9.4%) achieved incomplete response,and 6/96 (6.3%) occurred treatment failure.Compared to noncirrhotic patients,patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response (noncirrhosis 50/57 [87.7%] vs.cirrhosis 31/39 [79.5%],P =0.275),incomplete remission (noncirrhosis 4/57 [7.0%] vs.cirrhosis 5/39 [12.8%],P =0.338),and treatment failure (noncirrhosis 3/57 [5.3%] vs.cirrhosis 3/39 [7.7%],P =0.629).Importantly,the remission rate was comparable (54/57 [94.7%] and 36/39 [92.3%],P =0.629) for noncirrhotic and cirrhotic patients after immunosuppressive therapy.Compared to patients who maintained

  18. Dual monitoring using {sup 124}I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T. S.; Kim, J. H.; Kwon, H. C. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[{sup 124}I] iodouracil ({sup 124}I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ({sup 124}I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, {sup 124}I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, {sup 124}I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by {sup 124}I-FIAU PET imaging. {sup 124}I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. {sup 124}I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials.

  19. Design and Evaluation of Virtual Reality-Based Therapy Games with Dual Focus on Therapeutic Relevance and User Experience for Children with Cerebral Palsy.

    Science.gov (United States)

    Ni, Lian Ting; Fehlings, Darcy; Biddiss, Elaine

    2014-06-01

    Virtual reality (VR)-based therapy for motor rehabilitation of children with cerebral palsy (CP) is growing in prevalence. Although mainstream active videogames typically offer children an appealing user experience, they are not designed for therapeutic relevance. Conversely, rehabilitation-specific games often struggle to provide an immersive experience that sustains interest. This study aims to design and evaluate two VR-based therapy games for upper and lower limb rehabilitation and to evaluate their efficacy with dual focus on therapeutic relevance and user experience. Three occupational therapists, three physiotherapists, and eight children (8-12 years old), with CP Level I-III on the Gross Motor Function Classification System, evaluated two games for the Microsoft(®) (Redmond, WA) Kinect™ for Windows and completed the System Usability Scale (SUS), Physical Activity Enjoyment Scale (PACES), and custom feedback questionnaires. Children and therapists unanimously agreed on the enjoyment and therapeutic value of the games. Median scores on the PACES were high (6.24±0.95 on the 7-point scale). Therapists considered the system to be of average usability (50th percentile on the SUS). The most prevalent usability issue was detection errors distinguishing the child's movements from the supporting therapist's. The ability to adjust difficulty settings and to focus on targeted goals (e.g., elbow/shoulder extension, weight shifting) was highly valued by therapists. Engaging both therapists and children in a user-centered design approach enabled the development of two VR-based therapy games for upper and lower limb rehabilitation that are dually (a) engaging to the child and (b) therapeutically relevant.

  20. Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study

    Directory of Open Access Journals (Sweden)

    Altman Raul

    2012-01-01

    Full Text Available Abstract Background Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. Patients/methods In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT and the inhibition of platelet aggregation (IPA by light transmission aggregometry (LTA. Arachidonic acid (0.625 mmol/L and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L were used as platelet agonists. Results Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32. Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. Conclusion In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L.

  1. Short versus prolonged dual antiplatelet therapy duration after bare-metal stent implantation: 2-month landmark analysis from the CREDO-Kyoto registry cohort-2.

    Science.gov (United States)

    Natsuaki, Masahiro; Morimoto, Takeshi; Furukawa, Yutaka; Nakagawa, Yoshihisa; Kadota, Kazushige; Ando, Kenji; Shiomi, Hiroki; Toyota, Toshiaki; Watanabe, Hirotoshi; Ono, Koh; Shizuta, Satoshi; Tamura, Takashi; Inoko, Moriaki; Inada, Tsukasa; Shirotani, Manabu; Matsuda, Mitsuo; Aoyama, Takeshi; Onodera, Tomoya; Suwa, Satoru; Takeda, Teruki; Inoue, Katsumi; Kimura, Takeshi

    2016-09-19

    One-month duration of dual antiplatelet therapy (DAPT) has widely been adopted after bare-metal stent (BMS) implantation in the real clinical practice. However, it has not been adequately addressed yet whether DAPT for only 1-month could provide sufficient protection from ischemic events beyond 1-month after BMS implantation. We assessed the effects of short DAPT relative to prolonged DAPT on clinical outcomes with the landmark analysis at 2 month after BMS implantation. Among 13,058 consecutive patients enrolled in the CREDO-Kyoto registry cohort-2, this study population consisted of 4905 patients treated with BMS only in whom the information on the status of antiplatelet therapy was available at 2 month after stent implantation [single-antiplatelet therapy (SAPT) group: N = 2575 (acute myocardial infarction (AMI): N = 1257, and non-AMI: N = 1318), and DAPT group: N = 2330 (AMI: N = 1304, and non-AMI: N = 1026)]. Cumulative 3-year incidence of the primary outcome measure (a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, and GUSTO moderate/severe bleeding) was not significantly different between the SAPT and DAPT groups (9.8 versus 10.6 %, P = 0.34). After adjusting confounders, the risk of SAPT relative to DAPT for the primary outcome measure remained insignificant in the entire cohort (HR 0.97, 95 % CI 0.79-1.19, P = 0.77), and in both AMI and non-AMI strata without any significant interaction between clinical presentation (AMI versus non-AMI) and the effect of SAPT relative to DAPT (P interaction = 0.56). In conclusion, short DAPT <2 month after BMS implantation was as safe as prolonged DAPT ≥2-month in both AMI and non-AMI patients.

  2. Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (from the Patterns of Non-adherence to Anti-platelet Regimens In Stented Patients Registry).

    Science.gov (United States)

    Schoos, Mikkel; Chandrasekhar, Jaya; Baber, Usman; Bhasin, Aarti; Sartori, Samantha; Aquino, Melissa; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Kini, Annapoorna; Kruckoff, Mitchell; Moliterno, David; Henry, Timothy D; Weisz, Giora; Gibson, C Michael; Iakovou, Ioannis; Colombo, Antonio; Steg, P Gabriel; Witzenbichler, Bernhard; Chieffo, Alaide; Cohen, David; Stuckey, Thomas; Ariti, Cono; Dangas, George; Pocock, Stuart; Mehran, Roxana

    2017-09-15

    Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Macromolecular bipill of gemcitabine and methotrexate facilitates tumor-specific dual drug therapy with higher benefit-to-risk ratio

    DEFF Research Database (Denmark)

    Das, Manasmita; Jain, Roopal; Agrawal, Ashish Kumar

    2014-01-01

    ) spacer. Covalent conjugation of GEM and MTX via PEG linker not only transformed the solubility profiles of constituent drug molecules, but significantly improved their stability in the presence of plasma. In vitro cytotoxicity studies confirmed that GEM-PEG-MTX exerts higher cytotoxicity (IC50 0.181 μ......M at 24 h) in human breast adenocarcinoma MCF-7 cell lines, when compared to free drug congeners, i.e., free GEM (IC50 0.294 μM at 24 h) and free MTX (IC50 0.591 μM at 24 h). Tumor growth inhibition studies in chemically induced breast cancer bearing rats established the superiority of GEM......-PEG-MTX conjugate over all other pharmaceutical preparations including free drugs, physical mixture of GEM and MTX, and PEGylated GEM/MTX. Toxicity studies in tumor bearing rats as well as healthy mice corroborated that dual drug conjugation is an effective means to synergize the therapeutic indices of potential...

  4. Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

    Institute of Scientific and Technical Information of China (English)

    Fernando; Bessone; Melisa; Dirchwolf

    2016-01-01

    The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

  5. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)

    1995-01-01

    textabstractPrimary Biliary Cirrhosis (PBC) is a chronic, cholestatic liver disease characterized by non-suppurative destruction of interlobular and septal bile ducts, with subsequent liver damage and eventually development of cirrhosis. The disease is relatively rare with an estimated annual incide

  6. Local brain heavy ion irradiation induced Immunosuppression

    Science.gov (United States)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  7. Nonadherence to immunosuppression: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Moreso F

    2015-06-01

    Full Text Available Francesc Moreso,1 Irina B Torres,1 Gemma Costa-Requena,2 Daniel Serón1 1Nephrology Department, 2Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, Barcelona, Spain Abstract: Nonadherence to immunosuppressant treatment is common after renal transplantation involving >20% of patients. It is associated with cellular rejection, appearance of donor-specific antibodies, and chronic rejection. It has been estimated that nonadherence can be detected in approximately 50% of failing grafts. Since the evaluation of sociodemographic factors do not allow characterizing the target population, it is necessary to combine different measures of adherence (self-reporting and collateral reporting, pill counts, biological monitoring of blood samples, or others to increase its diagnostic accuracy. During the last decade, it has been shown that the implementation of a multidimensional intervention including information, motivation, and behavioral interventions may lead to an improvement of adherence to treatment. On the other hand, it has been shown that one-off feedback from a nurse, simplification of treatment, or financial assistance programs offered little improvement. Thus, increasing the effectiveness of adherence interventions might have a far greater impact on the long-term outcome of renal transplants than any improvement in specific medical treatments. This will require coordinated action from health professionals, researchers, health planners, and policy makers. Keywords: renal transplantation, nonadherence, immunosuppressive treatment

  8. Rat allotransplantation of epigastric microsurgical flaps: a study of rejection and the immunosuppressive effect of cyclosporin A

    Directory of Open Access Journals (Sweden)

    Carramaschi Fábio R.

    2000-01-01

    Full Text Available The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1 Wistar Furth isogenic donors and receptors (control set; (2 Brown Norway donors and Wistar Furth receptors (rejection set; and (3 Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set. Cyclosporin A (10 mg/kg/d treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.

  9. Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial.

    Science.gov (United States)

    Hess, Connie N; James, Stefan; Lopes, Renato D; Wojdyla, Daniel M; Neely, Megan L; Liaw, Danny; Hagstrom, Emil; Bhatt, Deepak L; Husted, Steen; Goodman, Shaun G; Lewis, Basil S; Verheugt, Freek W A; De Caterina, Raffaele; Ogawa, Hisao; Wallentin, Lars; Alexander, John H

    2015-08-18

    Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate. At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction)= 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction)= 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention. Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441

  10. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

    Science.gov (United States)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

    2012-07-05

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

  11. HIV-tuberculosis co-infection in an Indian scenario:The role of associated evidence of immunosuppression

    Institute of Scientific and Technical Information of China (English)

    Kushal Naha; Sowjanya Dasari; Mukhyaprana Prabhu

    2013-01-01

    Objective: To determine the relationship between tuberculosis and the degree of immunosuppression as determined by CD4 count. The impact of immunosuppression on the severity of tuberculosis was also studied. Methods: A retrospective analysis was performed in patients newly diagnosed with HIV infection and antiretroviral therapy (ART)-naive patients with known HIV seropositivity. All patients were diagnosed with active tuberculosis between January 2008 and December 2010, based on review of their medical records. Patients on chemoprophylaxis for opportunistic infection were excluded. Pattern and severity of tuberculosis, associated stigmata of immunosuppression, and CD4 counts were noted. Results: Of 140 patients satisfying the inclusion criteria, 52 had mild tuberculosis with no other evidence of immunosuppression, 52 had tuberculosis of variable severity with associated evidence of immunosuppression, and 36 had severe tuberculosis with no other evidence of immunosuppression. The CD4 count was highest in the first group [(109.2±99.9) cells/μL] and least in the second group [(58.4±39.8) cells/μL], and the difference was statistically significant (P=0.004). No statistical difference was observed in the CD4 count between those with mild tuberculosis and those with severe tuberculosis. Conclusions: In developing countries with a high prevalence of tuberculosis in the general population, the possibility of incidental tuberculosis in patients with HIV should always be considered. CD4 count does not appear to influence the severity of tuberculosis. The presence of concomitant evidence of immunosuppression in the form of category B and C conditions is indicative of underlying immunosuppression and associated with a significantly lower CD4 count.

  12. TOLERANCE IN ORGAN TRANSPLANTATION: FROM CONVENTIONAL IMMUNOSUPPRESSION TO EXTRACELLULAR VESICLES

    Directory of Open Access Journals (Sweden)

    Marta eMonguió-Tortajada

    2014-09-01

    Full Text Available Organ transplantation is often the unique solution for organ failure. However, rejection is still an unsolved problem. Although acute rejection is well controlled, the chronic use of immunosuppressive drugs for allograft acceptance causes numerous side effects in the recipient and do not prevent chronic allograft dysfunction. Different alternative therapies have been proposed to replace the classical treatment for allograft rejection. The alternative therapies are mainly based in pre-infusions of different types of regulatory cells, including DCs, MSCs and Tregs. Nevertheless, these approaches lack full efficiency and have many problems related to availability and applicability. In this context, the use of extracellular vesicles, and in particular exosomes, may represent a cell-free alternative approach in inducing transplant tolerance and survival. Preliminary approaches in vitro and in vivo have demonstrated the efficient alloantigen presentation and immunomodulation abilities of exosomes, leading to alloantigen-specific tolerance and allograft acceptance in rodent models. Donor exosomes have been used alone, processed by recipient antigen-presenting cells (APCs or administered together with suboptimal doses of immunesuppressive drugs, achieving specific allograft tolerance and infinite transplant survival. In this review we gathered the latest exosome-based strategies for graft acceptance and discuss the tolerance mechanisms involved in organ tolerance mediated by the administration of exosomes. We will also deal with the feasibility and difficulties that arise from the application of this strategy into the clinic.

  13. Pleurotus nebrodensis polysaccharide (PN-S) enhances the immunity of immunosuppressed mice.

    Science.gov (United States)

    Cui, Hai-Yan; Wang, Chang-Lu; Wang, Yu-Rong; Li, Zhen-Jing; Chen, Mian-Hua; Li, Feng-Juan; Sun, Yan-Ping

    2015-10-01

    In the present study, the effects of Pleurotus nebrodensis polysaccharide (PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and nitric oxide (NOS) in splenocytes. qRT-PCR results also indicated that PN-S increased the mRNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase (iNOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.

  14. The cost-effectiveness of dual oral antiplatelet therapy following percutaneous coronary intervention: a Swedish analysis of the CREDO trial.

    Science.gov (United States)

    Ringborg, Anna; Lindgren, Peter; Jönsson, Bengt

    2005-12-01

    The CREDO trial demonstrated the clinical efficacy of 12-month antiplatelet therapy with clopidogrel compared to standard 28-day treatment with a 27% relative reduction in the combined risk of death, myocardial infarction, or stroke in patients undergoing percutaneous coronary intervention (PCI) and being treated with aspirin. This study evaluated the long-term cost-effectiveness of 12-month vs. 28-day therapy with clopidogrel in Sweden. A Markov model was developed which assumed a hypothetical cohort of patients in a post-PCI state to have certain risks of suffering one of the endpoints of the CREDO trial: stroke, myocardial infarction, or death. The model predicted a mean survival of 12.098 years in the 12-month arm vs. 12.026 in the 28-day arm, an incremental gain of 0.072 life-years. The gain in survival came at a predicted incremental cost of Euro 217, resulting in an incremental cost-effectiveness ratio of Euro 3,022. Thus the predicted cost-effectiveness ratio of long-term treatment with clopidogrel in patients undergoing PCI is well below the threshold values currently considered cost-effective.

  15. Efficacy and safety of aliskiren-based dual and triple combination therapies in US minority patients with stage 2 hypertension.

    Science.gov (United States)

    Ferdinand, Keith C; Weitzman, Richard; Israel, Marc; Lee, Joleen; Purkayastha, Das; Jaimes, Edgar A

    2011-01-01

    Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m(2), 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine (P high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated. Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  16. Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with LPV/r+3TC for initial ART in HIV infected adults

    Directory of Open Access Journals (Sweden)

    Josép M Gatell

    2014-11-01

    Full Text Available Introduction: The National AIDS Plan and the Spanish AIDS study group (GESIDA panel of experts propose “preferred regimens” of antiretroviral treatment (ART as initial therapy in HIV-infected patients for 2013 [1]. All these regimens are triple therapy regimens. The Gardel Study assessed the efficacy and safety of a dual therapy (DT combination of lopinavir/ritonavir (LPV/r 400/100 mg BID+ lamivudine (3TC 150 mg BID [2]. The objective of this study is to evaluate the costs and efficiency of initiating treatment with the GESIDA “preferred regimens” and DT. Materials and Methods: Economic assessment of costs and efficiency (cost/efficacy through decision tree analysis models. Efficacy was defined as the probability of having viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance tests during the first 48 weeks. The payer perspective (Spanish National Health System was applied considering only differential direct costs: ART (official prizes, management of adverse effects, resistance tests, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: base, most favourable and most unfavourable cases. Results: In the base case scenario, the cost of initiating treatment ranges from 5138 euros for DT, to 12,059 euros for tenofovir DF/emtricitabine (TDF/FTC+raltegravir (RAL. The efficacy ranges between 0.66 for abacavir (ABC/3TC+LPV/r and ABC/3TC+atazanavir (ATV/r, and 0.88 for DT. Efficiency, in terms of cost/efficacy, varies between 5817 and 13,930 euros per responder at 48 weeks, for DT and TDF/FTC+RAL respectively. DT is the most efficient regimen in the most favourable (5503 euros per responder and most unfavourable (6169 euros per responder

  17. Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy.

    Science.gov (United States)

    Costa, Francesco; Tijssen, Jan G; Ariotti, Sara; Giatti, Sara; Moscarella, Elisabetta; Guastaroba, Paolo; De Palma, Rossana; Andò, Giuseppe; Oreto, Giuseppe; Zijlstra, Felix; Valgimigli, Marco

    2015-12-07

    Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24- and 6-month dual antiplatelet therapy groups. Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS-BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS-BLED. Major bleeding and transfusions were higher in the 24- versus 6-month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (Pint=0.05 and Pint=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24-month rather

  18. Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.

    Science.gov (United States)

    Zhang, Hong-Zhe; Kim, Moo Hyun; Han, Jin-Yeong; Jeong, Young-Hoon

    2014-01-01

    Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

  19. Immunosuppressive cells in tumor immune escape and metastasis.

    Science.gov (United States)

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

  20. Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy.

    Science.gov (United States)

    Chang, Yong S; Graves, Bradford; Guerlavais, Vincent; Tovar, Christian; Packman, Kathryn; To, Kwong-Him; Olson, Karen A; Kesavan, Kamala; Gangurde, Pranoti; Mukherjee, Aditi; Baker, Theresa; Darlak, Krzysztof; Elkin, Carl; Filipovic, Zoran; Qureshi, Farooq Z; Cai, Hongliang; Berry, Pamela; Feyfant, Eric; Shi, Xiangguo E; Horstick, James; Annis, D Allen; Manning, Anthony M; Fotouhi, Nader; Nash, Huw; Vassilev, Lyubomir T; Sawyer, Tomi K

    2013-09-03

    Stapled α-helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo. Specifically, ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities, shows submicromolar cellular activities in cancer cell lines in the presence of serum, and demonstrates highly specific, on-target mechanism of action. A high resolution (1.7-Å) X-ray crystal structure reveals its molecular interactions with the target protein MDMX, including multiple contacts with key amino acids as well as a role for the hydrocarbon staple itself in target engagement. Most importantly, ATSP-7041 demonstrates robust p53-dependent tumor growth suppression in MDM2/MDMX-overexpressing xenograft cancer models, with a high correlation to on-target pharmacodynamic activity, and possesses favorable pharmacokinetic and tissue distribution properties. Overall, ATSP-7041 demonstrates in vitro and in vivo proof-of-concept that stapled peptides can be developed as therapeutically relevant inhibitors of protein-protein interaction and may offer a viable modality for cancer therapy.

  1. Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients

    Science.gov (United States)

    Lee, Young Ki; Song, Sun Ok; Kim, Kwang Joon; Cho, Yongin; Choi, Younjeong; Yun, Yujung; Kang, Eun-Seok; Cha, Bong Soo; Lee, Hyun Chul

    2013-01-01

    Background This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D). Methods This prospective observational study was conducted across 24 weeks for drug-naïve Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%≤HbA1cpioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naïve Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels. PMID:24404518

  2. Phenylboronic acid-sugar grafted polymer architecture as a dual stimuli-responsive gene carrier for targeted anti-angiogenic tumor therapy.

    Science.gov (United States)

    Kim, Jinhwan; Lee, Yeong Mi; Kim, Hyunwoo; Park, Dongsik; Kim, Jihoon; Kim, Won Jong

    2016-01-01

    We present a cationic polymer architecture composed of phenylboronic acid (PBA), sugar-installed polyethylenimine (PEI), and polyethylene glycol (PEG). The chemical bonding of PBA with the diol in the sugar enabled the crosslinking of low-molecular-weight (MW) PEI to form high-MW PEI, resulting in strong interaction with anionic DNA for gene delivery. Inside the cell, the binding of PBA and sugar was disrupted by either acidic endosomal pH or intracellular ATP, so gene payloads were released effectively. This dual stimuli-responsive gene release drove the polymer to deliver DNA for high transfection efficiency with low cytotoxicity. In addition, PBA moiety with PEGylation facilitated the binding of polymer/DNA polyplexes to sialylated glycoprotein which is overexpressed on the tumor cell membrane, and thus provided high tumor targeting ability. Therapeutic application of our polymer was demonstrated as an anti-angiogenic gene delivery agent for tumor growth inhibition. Our judicious designed polymer structure based on PBA provides enormous potential as a gene delivery agent for effective gene therapy by stimuli-responsiveness and tumor targeting.

  3. Emerging role of dual antiplatelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma.

    Science.gov (United States)

    Aiolfi, Roberto; Sitia, Giovanni

    2014-01-01

    Platelets, the chief effectors of vascular homeostasis, have been identified as important players in the pathogenesis of both acute and chronic liver disease in preclinical models of hepatitis B viral infection. Platelets are thought to promote the accumulation of virus-specific T-cells into the liver parenchyma. Importantly, the inhibition of platelet activation by clinically relevant doses of aspirin and clopidogrel was able to reduce immune-mediated necroinflammatory liver disease, extracellular matrix deposition, and hepatocellular carcinoma development; the same treatment was able to improve overall survival. These results strongly support the design of clinical trials aiming to define the potential of antiplatelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma.

  4. Emerging role of dual antiplatelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Aiolfi R

    2014-11-01

    Full Text Available Roberto Aiolfi, Giovanni Sitia Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy Abstract: Platelets, the chief effectors of vascular homeostasis, have been identified as important players in the pathogenesis of both acute and chronic liver disease in preclinical models of hepatitis B viral infection. Platelets are thought to promote the accumulation of virus-specific T-cells into the liver parenchyma. Importantly, the inhibition of platelet activation by clinically relevant doses of aspirin and clopidogrel was able to reduce immune-mediated necroinflammatory liver disease, extracellular matrix deposition, and hepatocellular carcinoma development; the same treatment was able to improve overall survival. These results strongly support the design of clinical trials aiming to define the potential of antiplatelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma. Keywords: platelets, hepatocellular carcinoma, hepatitis B virus

  5. Prevention of avascular necrosis in displaced talar neck fractures by hyperbaric oxygenation therapy: A dual case report

    Directory of Open Access Journals (Sweden)

    Mei-Dan O

    2008-01-01

    Full Text Available Talar neck fractures are a rare injury that account for less then 2% of all foot fractures. Displaced fractures are associated with an exceedingly high rate of avascular necrosis (AVN. The incidence of AVN following Hawkins Type 3 fractures of the talar neck may approach 100%, particularly if diagnosis and reduction are delayed. Severe cases may present as pain and disability of the ankle and the subtalar joints due to a talar dome collapse, resulting in degenerative changes that usually require hind foot arthrodesis. We present two cases of traumatic displaced talar neck fractures which were treated surgically more than 2 weeks following injury due to a delay in diagnosis. Both patients underwent hyperbaric oxygen therapy (HBOT after the operation and neither resulted in AVN of the talus in a three-year follow-up. We suggest that this favorable result may be due to the beneficial effects of HBOT.

  6. High residual platelet reactivity during dual antiplatelet therapy, found by optical aggregometry and the rate of atherothrombotic complications after coronary artery stenting in patients with ischemic heart disease in clinical practice

    OpenAIRE

    N. F. Puchinyan; N. V. Furman; P. V. Dolotovskaya; L. L. Malinova

    2016-01-01

    Aim. To study the prevalence of high residual platelet reactivity (HRPR) during the dual antiplatelet therapy (DAT) with acetylsalicylic acid (ASA) and clopidogrel by optical aggregometry in patients with ischemic heart disease (IHD) after percutaneous transluminal coronary angioplasty (PTCA) in clinical practice, as well as to determine its value for the prediction of clinical course and outcome of disease.Material and methods. Patients after PTCA and during DAT were included into the study....

  7. Drug-Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation : A Review

    NARCIS (Netherlands)

    van Maarseveen, Erik M.; Rogers, Christin C.; Trofe-Clark, Jennifer; van Zuilen, Arjan D.; Mudrikova, Tania

    2012-01-01

    Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive ther

  8. Clinical aspects of immunosuppression in poultry

    Directory of Open Access Journals (Sweden)

    Rеsаnоvić Rаdmilа

    2015-01-01

    Full Text Available Immunity is ability to stop an infection. Immunosupression is a status where the immunity is reduced. Humoral (antibodies and/or cell immunity may be depressed. Immunosupression can be caused by infectious agents, improper feeding balance (deficiencies, lack of biosecurity, management failures, stress or by a combination of these factors. Each of these possible causes must be seriously worked out to prevent the consequences of immunosupression on profitability. Environmental factors and numerous infectious pathogens have been identified as a multi-factorial cause of various degrees of immunosupression. Mainly subclinical character and coinfections make the diagnosis of the primary immunosuppressive agents difficult. On the other hand, early diagnosis and identification of contributing factors are important to develop strategies to fight immunosupression in birds successfully. A combination of biosecurity measures, optimized housing condition and stress reduction together with appropriate vaccination strategies is necessary for the successful control of immunosupression in commercial poultry.

  9. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  10. Kidney transplant from a living monozygotic twin donor with no maintenance immunosuppression.

    Science.gov (United States)

    Sánchez-Escuredo, Ana; Barajas, Alberto; Revuelta, Ignacio; Blasco, Miquel; Cofan, Federic; Esforzado, Núria; Ricart, María José; Torregrosa, Vicens; Campistol, Josep Maria; Oppenheimer, Federic; Diekmann, Fritz

    2015-01-01

    From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

  11. Deriving concentrations of oxygen and carbon in human tissues using single- and dual-energy CT for ion therapy applications

    Science.gov (United States)

    Landry, Guillaume; Parodi, Katia; Wildberger, Joachim E.; Verhaegen, Frank

    2013-08-01

    Dedicated methods of in-vivo verification of ion treatment based on the detection of secondary emitted radiation, such as positron-emission-tomography and prompt gamma detection require high accuracy in the assignment of the elemental composition. This especially concerns the content in carbon and oxygen, which are the most abundant elements of human tissue. The standard single-energy computed tomography (SECT) approach to carbon and oxygen concentration determination has been shown to introduce significant discrepancies in the carbon and oxygen content of tissues. We propose a dual-energy CT (DECT)-based approach for carbon and oxygen content assignment and investigate the accuracy gains of the method. SECT and DECT Hounsfield units (HU) were calculated using the stoichiometric calibration procedure for a comprehensive set of human tissues. Fit parameters for the stoichiometric calibration were obtained from phantom scans. Gaussian distributions with standard deviations equal to those derived from phantom scans were subsequently generated for each tissue for several values of the computed tomography dose index (CTDIvol). The assignment of %weight carbon and oxygen (%wC,%wO) was performed based on SECT and DECT. The SECT scheme employed a HU versus %wC,O approach while for DECT we explored a Zeff versus %wC,O approach and a (Zeff, ρe) space approach. The accuracy of each scheme was estimated by calculating the root mean square (RMS) error on %wC,O derived from the input Gaussian distribution of HU for each tissue and also for the noiseless case as a limiting case. The (Zeff, ρe) space approach was also compared to SECT by comparing RMS error for hydrogen and nitrogen (%wH,%wN). Systematic shifts were applied to the tissue HU distributions to assess the robustness of the method against systematic uncertainties in the stoichiometric calibration procedure. In the absence of noise the (Zeff, ρe) space approach showed more accurate %wC,O assignment (largest error of

  12. First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system

    Science.gov (United States)

    Sportelli, G.; Belcari, N.; Camarlinghi, N.; Cirrone, G. A. P.; Cuttone, G.; Ferretti, S.; Kraan, A.; Ortuño, J. E.; Romano, F.; Santos, A.; Straub, K.; Tramontana, A.; Del Guerra, A.; Rosso, V.

    2014-01-01

    During particle therapy irradiation, positron emitters with half-lives ranging from 2 to 20 min are generated from nuclear processes. The half-lives are such that it is possible either to detect the positron signal in the treatment room using an in-beam positron emission tomography (PET) system, right after the irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since the activity distribution is spatially correlated with the dose, it is possible to use PET imaging as an indirect method to assure the quality of the dose delivery. In this work, we present a new dedicated PET system able to operate in-beam. The PET apparatus consists in two 10 cm × 10 cm detector heads. Each detector is composed of four scintillating matrices of 23 × 23 LYSO crystals. The crystal size is 1.9 mm × 1.9 mm × 16 mm. Each scintillation matrix is read out independently with a modularized acquisition system. The distance between the two opposing detector heads was set to 20 cm. The system has very low dead time per detector area and a 3 ns coincidence window, which is capable to sustain high single count rates and to keep the random counts relatively low. This allows a new full-beam monitoring modality that includes data acquisition also while the beam is on. The PET system was tested during the irradiation at the CATANA (INFN, Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with different doses and dose rates were analysed. In all cases the random to total coincidences ratio was equal or less than 25%. For each measurement we estimated the accuracy and precision of the activity range on a set of voxel lines within an irradiated PMMA phantom. Results show that the inclusion of data acquired during the irradiation, referred to as beam-on data, improves both the precision and accuracy of the range measurement with respect to data acquired only after irradiation. Beam-on data alone are enough to give precisions better than 1 mm

  13. Noninvasive theranostic imaging of HSV1-sr39TK-NTR/GCV-CB1954 dual-prodrug therapy in metastatic lung lesions of MDA-MB-231 triple negative breast cancer in mice.

    Science.gov (United States)

    Sekar, Thillai V; Foygel, Kira; Ilovich, Ohad; Paulmurugan, Ramasamy

    2014-01-01

    Metastatic breast cancer is an obdurate cancer type that is not amenable to chemotherapy regimens currently used in clinic. There is a desperate need for alternative therapies to treat this resistant cancer type. Gene-Directed Enzyme Prodrug Therapy (GDEPT) is a superior gene therapy method when compared to chemotherapy and radiotherapy procedures, proven to be effective against many types of cancer in pre-clinical evaluations and clinical trials. Gene therapy that utilizes a single enzyme/prodrug combination targeting a single cellular mechanism needs significant overexpression of delivered therapeutic gene in order to achieve therapy response. Hence, to overcome this obstacle we recently developed a dual therapeutic reporter gene fusion that uses two different prodrugs, targeting two distinct cellular mechanisms in order to achieve effective therapy with a limited expression of delivered transgenes. In addition, imaging therapeutic reporter genes offers additional information that indirectly correlates gene delivery, expression, and functional effectiveness as a theranostic approach. In the present study, we evaluate the therapeutic potential of HSV1-sr39TK-NTR fusion dual suicide gene therapy system that we recently developed, in MDA-MB-231 triple negative breast cancer lung-metastatic lesions in a mouse model. We compared the therapeutic potential of HSV1-sr39TK-NTR fusion with respective dual prodrugs GCV-CB1954 with HSV1-sr39TK/GCV and NTR/CB1954 single enzyme prodrug system in this highly resistant metastatic lesion of the lungs. In vitro optimization of dose and duration of exposure to GCV and CB1954 was performed in MDA-MB-231 cells. Drug combinations of 1 μg/ml GCV and 10 μM CB1954 for 3 days was found to be optimal regimen for induction of significant cell death, as assessed by FACS analysis. In vivo therapeutic evaluation in animal models showed a complete ablation of lung metastatic nodules of MDA-MB-231 triple negative breast cancer cells following

  14. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial.

    Science.gov (United States)

    Haidar, Ahmad; Legault, Laurent; Messier, Virginie; Mitre, Tina Maria; Leroux, Catherine; Rabasa-Lhoret, Rémi

    2015-01-01

    The artificial pancreas is an emerging technology for the treatment of type 1 diabetes and two configurations have been proposed: single-hormone (insulin alone) and dual-hormone (insulin and glucagon). We aimed to delineate the usefulness of glucagon in the artificial pancreas system. We did a randomised crossover trial of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy (continuous subcutaneous insulin infusion) in participants aged 12 years or older with type 1 diabetes. Participants were assigned in a 1:1:1:1:1:1 ratio with blocked randomisation to the three interventions and attended a research facility for three 24-h study visits. During visits when the patient used the single-hormone artificial pancreas, insulin was delivered based on glucose sensor readings and a predictive dosing algorithm. During dual-hormone artificial pancreas visits, glucagon was also delivered during low or falling glucose. During conventional insulin pump therapy visits, patients received continuous subcutaneous insulin infusion. The study was not masked. The primary outcome was the time for which plasma glucose concentrations were in the target range (4·0-10·0 mmol/L for 2 h postprandially and 4·0-8·0 mmol/L otherwise). Hypoglycaemic events were defined as plasma glucose concentration of less than 3·3 mmol/L with symptoms or less than 3·0 mmol/L irrespective of symptoms. Analysis was by modified intention to treat, in which we included data for all patients who completed at least two visits. A p value of less than 0·0167 (0·05/3) was regarded as significant. This trial is registered with ClinicalTrials.gov, number NCT01754337. The mean proportion of time spent in the plasma glucose target range over 24 h was 62% (SD 18), 63% (18), and 51% (19) with single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional insulin pump therapy, respectively. The mean difference in time spent in the target

  15. Dual Pressure from Antiretroviral Therapy and Cell-Mediated Immune Response on the Human Immunodeficiency Virus Type 1 Protease Gene

    Science.gov (United States)

    Karlsson, Annika C.; Deeks, Steven G.; Barbour, Jason D.; Heiken, Brandon D.; Younger, Sophie R.; Hoh, Rebecca; Lane, Meghan; Sällberg, Matti; Ortiz, Gabriel M.; Demarest, James F.; Liegler, Teri; Grant, Robert M.; Martin, Jeffrey N.; Nixon, Douglas F.

    2003-01-01

    Human immunodeficiency virus (HIV)-specific CD8+ T-lymphocyte pressure can lead to the development of viral escape mutants, with consequent loss of immune control. Antiretroviral drugs also exert selection pressures on HIV, leading to the emergence of drug resistance mutations and increased levels of viral replication. We have determined a minimal epitope of HIV protease, amino acids 76 to 84, towards which a CD8+ T-lymphocyte response is directed. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. Among 29 HIV-infected patients who were treated with protease inhibitors and who had developed resistance to these drugs, we show that the wild-type PR82V76-84 epitope is commonly recognized by cytotoxic T lymphocytes (CTL) in HLA-A2-positive patients and that the CTL directed to this epitope are of high avidity. In contrast, the mutant PR82A76-84 epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. Paradoxically, the absence of a mutation at position 82 was associated with the presence of a high-avidity CD8+ T-cell response to the wild-type virus sequence. Our results indicate that both HIV type 1-specific CD8+ T cells and antiretroviral drugs provide complex pressures on the same amino acid sequence of the HIV protease gene and, thus, can influence viral sequence evolution. PMID:12767994

  16. Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats.

    Science.gov (United States)

    Lueckemann, Laura; Bösche, Katharina; Engler, Harald; Schwitalla, Jan-Claudius; Hadamitzky, Martin; Schedlowski, Manfred

    2016-01-01

    In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome.

  17. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  18. Posterior Reversible Encephalopathy Syndrome and Fatal Cryptococcal Meningitis After Immunosuppression in a Patient With Elderly Onset Inflammatory Bowel Disease

    Science.gov (United States)

    Vasant, Dipesh H.; Limdi, Jimmy K.; Borg-Bartolo, Simon P.; Bonington, Alec

    2016-01-01

    Advanced age and associated comorbidities are-recognized predictors of life-threatening adverse outcomes, such as opportunistic infection following immunosuppressive therapy. We describe the case of an elderly patient with stricturing colonic Crohn’s disease and significant clinical comorbidities, initially controlled with corticosteroid induction followed by infliximab, whose course was complicated by fatal disseminated cryptococcal infection and posterior reversible encephalopathy syndrome. Our patient’s case highlights rare, but serious, complications of immunosuppression. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this potentially vulnerable group, maximizing benefit and minimizing harm.

  19. Efficacy and safety of short-term dual- versus mono-antiplatelet therapy in patients with ischemic stroke or TIA: a meta-analysis of 10 randomized controlled trials.

    Science.gov (United States)

    Liu, Yang; Fei, Zhaoxia; Wang, Wei; Fang, Jingxue; Zou, Meijuan; Cheng, Gang

    2016-11-01

    Stroke is still a primary disease for death and disability all over the world. The optimal antiplatelet therapy for treatment of stroke is under controversy. We performed a meta-analysis to justify whether short-term (≤1 year) dual-antiplatelet therapy (DAPT) has advantages over mono-antiplatelet therapy. We systematically searched the databases of Cochrane library, Pubmed and Embase up to July 2016. Randomized controlled trials (RCTs) comparing DAPT with mono-antiplatelet therapy were included in our meta-analysis. Totally ten trials involving 8969 patients were satisfied with our inclusion criteria. At the end of follow-up, DAPT is associated with a significant reduction in recurrent stroke [risk ratio (RR) 0.65, 95 % confidence interval (CI) 0.56-0.76, P antiplatelet therapy. The subgroup analysis according to different races, antiplatelet combinations or initiation time produced similar outcomes as comprehensive outcomes. Given short-term treatment regimen, DAPT can be superior to mono-antiplatelet therapy in treating IS or transient ischemic attack (TIA). No matter in acute or non-acute phase of IS, short-term DAPT has more efficacy than mono-antiplatelet therapy and has equivalent safety as mono-antiplatelet therapy.

  20. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Kirby Sean

    2012-03-01

    Full Text Available Abstract Background After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications. Methods A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications. Results The incidence of neoplasia on lung biopsy was 0.4% (9 cases, which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases, and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2% cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03. Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns. Conclusions Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with

  1. Food safety for the solid organ transplant patient: preventing foodborne illness while on chronic immunosuppressive drugs.

    Science.gov (United States)

    Obayashi, Patricia A C

    2012-12-01

    Issues regarding food safety are seen increasingly in the news; outbreaks of foodborne illness have been associated with public health concerns ranging from mild illness to death. For the solid organ transplant patient, immunosuppressive and antibacterial drugs, which maintain transplant organ function, can expose the transplant patient to increased risk of foodborne illness from bacteria, viruses, fungi, and parasites. This review article describes the clinical consequences, sources of foodborne illness, and food safety practices needed to minimize risks to the solid organ transplant patient who must take lifelong immunosuppressive drugs. All members of the transplant team share responsibility for education of the solid organ transplant patient in preventing infections. The registered dietitian, as part of the transplant team, is the recognized expert in providing food safety education in the context of medical nutrition therapy to solid organ transplant patients, the patients' caregivers, and other healthcare providers.

  2. Collagenase enzymatic fasciotomy for Dupuytren contracture in patients on chronic immunosuppression.

    Science.gov (United States)

    Waters, Michael J; Belsky, Mark R; Blazar, Philip E; Leibman, Matthew I; Ruchelsman, David E

    2015-11-01

    Collagenase enzymatic fasciotomy is an accepted nonsurgical treatment for disabling hand contractures caused by Dupuytren disease. We conducted a study to investigate use of collagenase in an immunosuppressed population. We retrospectively reviewed data from 2 academic hand surgical practices. Eight patients on chronic immunosuppressive therapies were treated with collagenase for digital contractures between 2010 and 2011. Thirteen collagenase enzymatic fasciotomies were performed in these 8 patients. Mean preinjection contracture was 53.0°. At mean follow-up of 6.7 months, mean magnitude of contracture improved to 12.9°. Mean metacarpophalangeal joint contracture improved from 42.0° to 4.2°. Mean proximal interphalangeal joint contracture improved from 65.8° to 21.7°. Three of the enzymatic fasciotomies were complicated by skin tears. There were no infections. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated prospectively.

  3. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    Science.gov (United States)

    Högerle, Benjamin A; Kohli, Neeraj; Habibi-Parker, Kirsty; Lyster, Haifa; Reed, Anna; Carby, Martin; Zeriouh, Mohamed; Weymann, Alexander; Simon, André R; Sabashnikov, Anton; Popov, Aron-Frederik; Soresi, Simona

    2016-03-01

    Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

  4. Predictors of Immunosuppressive Regulatory T Lymphocytes in Healthy Women

    Directory of Open Access Journals (Sweden)

    Shalaka S. Hampras

    2012-01-01

    Full Text Available Immunosuppressive regulatory T (Treg cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and BioRepository (DBBR program at Roswell Park Cancer Institute (RPCI, Buffalo, NY, USA. Peripheral blood levels of CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI, and hormone replacement therapy (HRT were found to be significant positive predictors of Treg cell levels in peripheral blood (P≤0.05. Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (P<0.05 negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.

  5. Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

    Science.gov (United States)

    Yang, Fu-Qiang; Rao, Gui-Rong; Wang, Gui-Qiang; Li, Yue-Qi; Xie, Yao; Zhang, Zhan-Qing; Deng, Cun-Liang; Mao, Qing; Li, Jun; Zhao, Wei; Wang, Mao-Rong; Han, Tao; Chen, Shi-Jun; Pan, Chen; Tan, De-Ming; Shang, Jia; Zhang, Ming-Xiang; Zhang, Yue-Xin; Yang, Ji-Ming; Chen, Guang-Ming

    2017-01-01

    AIM To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy. PMID:28127204

  6. SU-E-J-19: Accuracy of Dual-Energy CT-Derived Relative Electron Density for Proton Therapy Dose Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Mullins, J; Duan, X; Kruse, J; Herman, M [Mayo Clinic, Rochester, MN (United States); Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States)

    2014-06-01

    Purpose: To determine the suitability of dual-energy CT (DECT) to calculate relative electron density (RED) of tissues for accurate proton therapy dose calculation. Methods: DECT images of RED tissue surrogates were acquired at 80 and 140 kVp. Samples (RED=0.19−2.41) were imaged in a water-equivalent phantom in a variety of configurations. REDs were calculated using the DECT numbers and inputs of the high and low energy spectral weightings. DECT-derived RED was compared between geometric configurations and for variations in the spectral inputs to assess the sensitivity of RED accuracy versus expected values. Results: RED accuracy was dependent on accurate spectral input influenced by phantom thickness and radius from the phantom center. Material samples located at the center of the phantom generally showed the best agreement to reference RED values, but only when attenuation of the surrounding phantom thickness was accounted for in the calculation spectra. Calculated RED changed by up to 10% for some materials when the sample was located at an 11 cm radius from the phantom center. Calculated REDs under the best conditions still differed from reference values by up to 5% in bone and 14% in lung. Conclusion: DECT has previously been used to differentiate tissue types based on RED and Z for binary tissue-type segmentation. To improve upon the current standard of empirical conversion of CT number to RED for treatment planning dose calculation, DECT methods must be able to calculate RED to better than 3% accuracy throughout the image. The DECT method is sensitive to the accuracy of spectral inputs used for calculation, as well as to spatial position in the anatomy. Effort to address adjustments to the spectral calculation inputs based on position and phantom attenuation will be required before DECT-determined RED can achieve a consistent level of accuracy for application in dose calculation.

  7. Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

    Institute of Scientific and Technical Information of China (English)

    Zheng-hong QIN; Lu-yang TAO; Xin CHEN

    2007-01-01

    NF-κB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-κB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-κB on cell survival could be protec- tive or destructive, depending on types, developmental stages of cells, and patho- logical conditions. The complexity of NF-rd3 in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-κB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly as- sociated with the inhibition of NF-r,B, leading to speculation that blocking the pathological activation of NF-κB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-κB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-κB that are involved in cell death and survival to elucidate why NF-r,B promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-κB inhibitors on neuroprotection in certain pathological conditions to specu- late if NF-κB is a potential target for neuroprotective therapy.

  8. Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

    Science.gov (United States)

    Melloni, Chiara; Washam, Jeffrey B; Jones, W Schuyler; Halim, Sharif A; Hasselblad, Victor; Mayer, Stephanie B; Heidenfelder, Brooke L; Dolor, Rowena J

    2015-01-01

    Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted. © 2015 American Heart Association, Inc.

  9. Retrospective, nonrandomized controlled study on autoadjusting, dual-pressure positive airway pressure therapy for a consecutive series of complex insomnia disorder patients

    Science.gov (United States)

    Krakow, Barry; McIver, Natalia D; Ulibarri, Victor A; Nadorff, Michael R

    2017-01-01

    Purpose Emerging evidence shows that positive airway pressure (PAP) treatment of obstructive sleep apnea (OSA) and upper airway resistance syndrome (UARS) in chronic insomnia patients (proposed “complex insomnia” disorder) leads to substantial decreases in insomnia severity. Although continuous PAP (CPAP) is the pressure mode most widely researched, intolerance to fixed pressurized air is rarely investigated or described in comorbidity patients. This retrospective study examined dual pressure, autoadjusting PAP modes in chronic, complex insomnia disorder patients. Patients and methods Chronic insomnia disorder patients (mean [SD] insomnia severity index [ISI] =19.11 [3.34]) objectively diagnosed with OSA or UARS and using either autobilevel PAP device or adaptive servoventilation (ASV) device after failing CPAP therapy (frequently due to intolerance to pressurized air, poor outcomes, or emergence of CSA) were divided into PAP users (≥20 h/wk) and partial users (insomnia patients, PAP users (n=246) averaged 6.10 (1.78) nightly hours and 42.71 (12.48) weekly hours and partial users (n=56) averaged 1.67 (0.76) nightly hours and 11.70 (5.31) weekly hours. For mean (SD) decreases in total ISI scores, a significant (group × time) interaction was observed (F[1,300]=13.566; Pinsomnia symptoms (r=−0.256, PInsomnia severity significantly decreased in patients using autoadjusting PAP devices, but the study design restricts interpretation to an association. Future research must elucidate the interaction between insomnia and OSA/UARS as well as the adverse influence of pressure intolerance on PAP adaptation in complex insomnia patients. Randomized controlled studies must determine whether advanced PAP modes provide benefits over standard CPAP modes in these comorbidity patients. PMID:28331381

  10. Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial.

    Science.gov (United States)

    Haidar, Ahmad; Legault, Laurent; Matteau-Pelletier, Laurence; Messier, Virginie; Dallaire, Maryse; Ladouceur, Martin; Rabasa-Lhoret, Rémi

    2015-08-01

    Additional benefits of the dual-hormone (insulin and glucagon) artificial pancreas compared with the single-hormone (insulin alone) artificial pancreas have not been assessed in young people in outpatient unrestricted conditions. We evaluated the efficacy of three systems for nocturnal glucose control in children and adolescents with type 1 diabetes. We did a randomised, three-way, crossover trial in children aged 9-17 years with type 1 diabetes attending a diabetes camp in Canada. With use of sealed envelopes, children were randomly assigned in a 1:1:1:1:1:1 ratio with blocks of six to different sequences of the three interventions (single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional continuous subcutaneous insulin pump therapy). Each intervention was applied for 3 consecutive nights. Participants, study staff, and endpoint assessors were not masked. The primary outcome was the percentage of time spent with glucose concentrations lower than 4·0 mmol/L from 2300 h to 0700 h. Analysis was by intention to treat. A p value of less than 0·0167 was regarded as significant. This study is registered with ClinicalTrials.gov, number NCT02189694. Between June 30, 2014, and Aug 9, 2014, we enrolled 33 children of mean age 13·3 years (SD 2·3; range 9-17). The time spent at a glucose concentration lower than 4·0 mmol/L was median 0% (IQR 0·0-2·4) during nights with the dual-hormone artificial pancreas, 3·1% (0·0-6·9) during nights with the single-hormone artificial pancreas (p=0·032), and 3·4% (0-11·0) during nights with conventional pump therapy (p=0·0048 compared with dual-hormone artificial pancreas and p=0·32 compared with single-hormone artificial pancreas). 15 hypoglycaemic events (pump therapy compared with four events with the single-hormone system and no events with the dual-hormone system. None of the assessed outcomes varied with the order in which children and young adults were assigned interventions. The dual

  11. Short- versus standard-term dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation: A meta-analysis.

    Science.gov (United States)

    Basaraba, Jade E; Barry, Arden R

    2017-01-01

    Twelve months of dual antiplatelet therapy (DAPT) is recommended after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. However, certain clinical scenarios may require premature discontinuation of therapy (e.g. urgent surgical procedure, major bleeding). The objective of this systematic review and meta-analysis was to investigate clinically relevant outcomes associated with a shorter duration of DAPT after PCI with DES implantation. A systematic search of Medline and Embase (inception to December 2015) was conducted. Included were randomized controlled trials that compared 6 months (or less) of DAPT (defined as acetylsalicylic acid 75-200mg daily and a P2Y12 inhibitor) to the standard of 12 months. Outcomes of interest included death (all-cause and cardiac), myocardial infarction (MI), definite/probable stent thrombosis, and bleeding (major and overall). An odds ratio (OR) and 95% confidence interval (CI) were calculated for each outcome using a random effects model. Six trials (five open-label, one double-blind) were included (N=13,900). Four studies investigated 6 months of DAPT, and two studies investigated 3 months. Median follow-up was 12 months. There was no statistically significantly difference between groups regarding all-cause death (OR 0.88, 95% CI 0.64-1.20), cardiac death (OR 1.00, 95% CI 0.64-1.55), MI (OR 1.16, 95% CI 0.87-1.56), and stent thrombosis (OR 1.22, 95% CI 0.70-2.15). Both major and any bleeding were significantly decreased with shorter-term DAPT (OR 0.58, 95% CI 0.34-0.98, and OR 0.62, 95% CI 0.47-0.81, respectively). Shorter duration (3-6 months) of DAPT, as compared to 12 months, was not associated with a higher risk of death, MI, or stent thrombosis, but a lower rate of major and overall bleeding. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  12. Low density lipoprotein receptor targeted doxorubicin/DNA-Gold Nanorods as a chemo- and thermo-dual therapy for prostate cancer.

    Science.gov (United States)

    Zhang, Nan; Li, Shasha; Hua, Haiying; Liu, Dan; Song, Lili; Sun, Pengchao; Huang, Weiwei; Tang, Yafang; Zhao, Yongxing

    2016-11-20

    , all results consistently indicated that DNA-GNRs-PEG/R was able to increase in vitro and in vivo anti-cancer efficacy of DOX. With additional NIR laser treatment, GNRs produced heat and further enhanced the anti-cancer effect achieved by DOX/DNA-GNRs-PEG/R. Therefore, the chemo- and thermo-dual therapy could be a potential combined therapy for more efficient anti-cancer treatment in clinical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology.

    Science.gov (United States)

    Barillà, Francesco; Pelliccia, Francesco; Borzi, Mauro; Camici, Paolo; Cas, Livio Dei; Di Biase, Matteo; Indolfi, Ciro; Mercuro, Giuseppe; Montemurro, Vincenzo; Padeletti, Luigi; Filardi, Pasquale Perrone; Vizza, Carmine D; Romeo, Francesco

    2017-01-01

    Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to

  14. Comparing the clinical outcomes in patients with atrial fibrillation receiving dual antiplatelet therapy and patients receiving an addition of an anticoagulant after coronary stent implantation

    Science.gov (United States)

    Chaudhary, Nabin; Bundhun, Pravesh Kumar; Yan, He

    2016-01-01

    Abstract Background: Data regarding the clinical outcomes in patients with atrial fibrillation (AF) receiving dual antiplatelet therapy (DAPT) and an anticoagulant in addition to DAPT (DAPT + vitamin K antagonist [VKA]) after coronary stent implantation are still controversial. Therefore, in order to solve this issue, we aim to compare the adverse clinical outcomes in AF patients receiving DAPT and DAPT + VKA after percutaneous coronary intervention and stenting (PCI-S). Methods: Observational studies comparing the adverse clinical outcomes such as major bleeding, major adverse cardiovascular events, stroke, myocardial infarction, all-cause mortality, and stent thrombosis (ST) in AF patients receiving DAPT + VKA therapy, and DAPT after PCI-S have been searched from Medline, EMBASE, and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables, and the pooled analyses were performed with RevMan 5.3. Results: Eighteen studies consisting of a total of 20,456 patients with AF (7203 patients received DAPT + VKA and 13,253 patients received DAPT after PCI-S) were included in this meta-analysis. At a mean follow-up period of 15 months, the risk of major bleeding was significantly higher in DAPT + VKA group, with OR 0.62 (95% CI 0.50–0.77, P < 0.0001). There was no significant differences in myocardial infarction and major adverse cardiovascular event between DAPT + VKA and DAPT, with OR 1.27 (95% CI 0.92–1.77, P = 0.15) and OR 1.17 (95% CI 0.99–1.39, P = 0.07), respectively. However, the ST, stroke, and all-cause mortality were significantly lower in the DAPT + VKA group, with OR 1.98 (95% CI 1.03–3.81, P = 0.04), 1.59 (95% CI 1.08–2.34, P = 0.02), and 1.41 (95% CI 1.03–1.94, P = 0.03), respectively. Conclusion: At a mean follow-up period of 15 months, DAPT + VKA was associated with significantly lower risk of stroke, ST, and

  15. Imunossupressores na Dermatologia Immunosuppressive agents in Dermatology

    Directory of Open Access Journals (Sweden)

    Aline Lopes Bressan

    2010-02-01

    Full Text Available Os imunossupressores são drogas que agem na divisão celular e têm propriedades anti-inflamatórias. Sendo assim, são essencialmente prescritos na prevenção de rejeição de transplantes e no tratamento das doenças autoimunes e inflamatórias crônicas, que, na Dermatologia, têm a psoríase como maior representante. Nesta sessão serão descritas as principais drogas imunossupressoras, com orientações para seu manejo adequado.Immunosupressants are drugs that act in cell division and have anti-inflammatory effects. Therefore, they are essentially prescribed in the prevention of transplant rejection and in the treatment of autoimmune disorders and chronic inflammatory diseases, whose main example in Dermatology is psoriasis. In this work the most important immunosuppressive drugs and orientation to properly administer them are going to be described.

  16. Renoprotective strategies in lupus nephritis: beyond immunosuppression.

    Science.gov (United States)

    Griffin, B; Lightstone, L

    2013-10-01

    Lupus nephritis needs to be diagnosed promptly and treated specifically with appropriate immunosuppression. However, all patients with lupus nephritis have by definition chronic kidney disease (CKD) as they will have proteinuria with varying degrees of renal impairment. CKD requires careful additional management, not only to reduce the risk of progression to end-stage renal disease but also because it is probably the strongest risk for cardiovascular morbidity and mortality. This review focuses on the evidence underscoring strategies to prevent progression of CKD beyond the "simple" treatment of the lupus nephritis. The strategies include immaculate control of blood pressure, inhibition of the renin-angiotensin system to reduce blood pressure and proteinuria, and the benefits of lifestyle modifications such as tackling smoking, obesity and exercise. We also review the literature on control of dyslipidaemias which, although clearly of cardiovascular benefit, provide less compelling data for offering renoprotection. We touch on the emerging area of the importance of controlling urate levels in protecting against progressive renal impairment. Finally, there is a reminder about the importance of considering the nephrotoxicity of all medications prescribed for patients with lupus nephritis - above all the need to avoid the use of non-steroidal anti-inflammatory drugs. Overall, the theme is that there is much more to the management of patients with lupus nephritis than "just" the nephritis - a multidisciplinary approach involving nephrologists as well as rheumatologists is more likely to provide the appropriate wider care required for all patients with lupus nephritis.

  17. Immunosuppression during Rhizobium-legume symbiosis.

    Science.gov (United States)

    Luo, Li; Lu, Dawei

    2014-01-01

    Rhizobium infects host legumes to elicit new plant organs, nodules where dinitrogen is fixed as ammonia that can be directly utilized by plants. The nodulation factor (NF) produced by Rhizobium is one of the determinant signals for rhizobial infection and nodule development. Recently, it was found to suppress the innate immunity on host and nonhost plants as well as its analogs, chitins. Therefore, NF can be recognized as a microbe/pathogen-associated molecular pattern (M/PAMP) like chitin to induce the M/PAMP triggered susceptibility (M/PTS) of host plants to rhizobia. Whether the NF signaling pathway is directly associated with the innate immunity is not clear till now. In fact, other MAMPs such as lipopolysaccharide (LPS), exopolysaccharide (EPS) and cyclic-β-glucan, together with type III secretion system (T3SS) effectors are also required for rhizobial infection or survival in leguminous nodule cells. Interestingly, most of them play similarly negative roles in the innate immunity of host plants, though their signaling is not completely elucidated. Taken together, we believe that the local immunosuppression on host plants induced by Rhizobium is essential for the establishment of their symbiosis.

  18. Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential

    Directory of Open Access Journals (Sweden)

    Jeffery J. Auletta

    2011-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs possess immunomodulatory properties that make them attractive therapeutic alternatives. We evaluated the in vitro immunosuppressive activity of medium conditioned by human MSCs from 5 donors expanded 13 passages with or without FGF-2. FGF-2 supplementation increased expansion 3,500- and 240,000-fold by passages 7 and 13, respectively. There were no differences in immunosuppressive activity between media conditioned by passage-matched cells expanded under different conditions, but media conditioned by FGF-treated MSCs were superior to population doubling-matched controls. The immunosuppressive activity was maintained in three of the preparations but decreased with expansion in two. The proliferation induced by FGF-2 did not result in loss of immunosuppressive activity. However, because the immunosuppressive activity was not consistently preserved, caution must be exercised to ensure that the activity of the cells is sufficient after extensive expansion.

  19. Septic arthritis in immunocompetent and immunosuppressed hosts.

    Science.gov (United States)

    Wang, Dingyuan Alvin; Tambyah, Paul Anantharajah

    2015-04-01

    Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.

  20. 来氟米特用于抢救性治疗减免免疫抑制剂无效的肾移植术后 BK 病毒性肾病的体会:附4例报告%Experience with the application of leflunomide in rescuing therapy of BK virus nephropathy after renal transplantation in the case of ineffective treatment with reduction of immunosuppressant:report of 4 cases

    Institute of Scientific and Technical Information of China (English)

    范宇; 李纪岗; 钱叶勇; 石炳毅; 解俊杰

    2016-01-01

    目的:探讨抢救性应用来氟米特治疗减免免疫抑制剂无效的肾移植术后 BK 病毒性肾病(BKVN)的临床体会。方法4例肾移植术后 BKVN 受者,于术后第135~737日确诊,病理分期 A1期2例、B1期1例、B2期1例。均在减免免疫抑制剂治疗0.5~3.0个月无效后,采用来氟米特抢救性治疗,先予50 mg/d连用3 d,达到有效治疗血药浓度后应用20 mg/d 维持,观察其疗效及安全性。结果经过平均6个月(5~7个月)的随访,有效控制 BKVN 进展者3例,无效者1例(B2期)。服药过程中未发生明显不良反应。结论肾移植术后 BKVN,在减免免疫抑制剂无效时,抢救性应用来氟米特有可能减缓 BKVN 进展,减少移植肾丢失的发生率。及早发现和诊断 BKVN,力求病理学分期较早的情况下及时采取有效治疗措施效果较佳。%Objective To explore the clinical application experience of leflunomide in rescuing therapy of BK virus nephropathy (BKVN ) after renal transplantation in the case of ineffective treatment with reduction of immunosuppressant.Methods Four recipients with BKVN after renal transplantation were diagnosed at 1 35 th-737 th day after operation,with the pathological staging as following:2 cases in stage A1 ,1 case in stage B1 and 1 case in stage B2.For all recipients, leflunomide was used for rescuing therapy due to ineffective treatment with reduction of immunosuppressant for 0.5-3.0 months.Initially,50 mg/d of leflunomide was given continuously for 3 days,so as to reach therapeutic serum concentration,and then 20 mg/d of leflunomide was given for maintaining.The efficacy and safety were observed.Results After a follow-up for an average of 6 months (5-7 months),3 recipients with development of BKVN were controlled effectively,1 recipient (stage B2)with ineffective treatment.No obvious adverse reactions occurred during medication.Conclusions It is possible to slow down the development

  1. Immunosuppressive T-cell antibody induction for heart transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Gustafsson, Finn

    2013-01-01

    Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

  2. Comprehensive comparison of three different immunosuppressive regimens for liver transplant patients with hepatocellular carcinoma: steroid-free immunosuppression, induction immunosuppression and standard immunosuppression.

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Liu

    Full Text Available The different choices of immunosuppression (IS regimens influenced the outcomes of liver transplantation. Steroid was applied as a standard IS to prevent and treat rejections. However, steroid-related complications were increasingly prominent. This study compared the efficacy and safety of standard IS regimens with the efficacy and safety of steroid-free IS regimen and induction IS regimen in Chinese liver transplantation recipients for hepatocellular carcinoma (HCC. A total of 329 patients who underwent liver transplantation from January 2008 to December 2012 were retrospectively reviewed. Three different groups of patients received standard triple-drug IS regimen of steroid, tacrolimus (TAC and mycophenolate mofetil (MMF (triple-drug regimen group; n=57, induction-contained IS regimen of basiliximab, steroid, TAC and MMF (BS group; n=241, and induction-contained and steroid-free regimen of basiliximab, TAC and MMF (SF group; n=31, respectively. There were no significant differences in terms of patient, tumor-free and graft survival rates. The acute rejection rate and rejection time were equivalent in different groups. But compared with BS group, higher incidences of biliary complications (11.52% vs. 30.77%, p=0.013 and graft dysfunction (0.48% vs. 13.64%, p=0.003 were observed in SF group. Furthermore, compared with the two groups, incidence of pleural effusion was also higher in SF group (15.79%, 11.96% vs. 45.45%, respectively, both p<0.01. And a trend towards less proportion of De novo diabetes was revealed in SF group. Although it was found that patient, tumor-free and graft survival rates were equivalent among three IS regimens, higher incidences of complications were demonstrated in steroid-free regimen in patients for HCC. These findings suggested that steroid-free IS regimen has no clear advantages in comparison with standard IS regimens for liver transplant recipients with HCC and the postoperative complications should be treated with

  3. Evaluation of dual energy quantitative CT for determining the spatial distributions of red marrow and bone for dosimetry in internal emitter radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Goodsitt, Mitchell M., E-mail: goodsitt@umich.edu; Shenoy, Apeksha; Howard, David; Christodoulou, Emmanuel; Dewaraja, Yuni K. [Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109 (United States); Shen, Jincheng [Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, Michigan 48109 (United States); Schipper, Matthew J. [Department of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109 (United States); Wilderman, Scott [Department of Nuclear Engineering, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109 (United States); Chun, Se Young [Ulsan National Institute of Science and Technology (UNIST), School of Electrical and Computer Engineering, Ulsan 689-798 (Korea, Republic of)

    2014-05-15

    Purpose: To evaluate a three-equation three-unknown dual-energy quantitative CT (DEQCT) technique for determining region specific variations in bone spongiosa composition for improved red marrow dose estimation in radionuclide therapy. Methods: The DEQCT method was applied to 80/140 kVp images of patient-simulating lumbar sectional body phantoms of three sizes (small, medium, and large). External calibration rods of bone, red marrow, and fat-simulating materials were placed beneath the body phantoms. Similar internal calibration inserts were placed at vertebral locations within the body phantoms. Six test inserts of known volume fractions of bone, fat, and red marrow were also scanned. External-to-internal calibration correction factors were derived. The effects of body phantom size, radiation dose, spongiosa region segmentation granularity [single (∼17 × 17 mm) region of interest (ROI), 2 × 2, and 3 × 3 segmentation of that single ROI], and calibration method on the accuracy of the calculated volume fractions of red marrow (cellularity) and trabecular bone were evaluated. Results: For standard low dose DEQCT x-ray technique factors and the internal calibration method, the RMS errors of the estimated volume fractions of red marrow of the test inserts were 1.2–1.3 times greater in the medium body than in the small body phantom and 1.3–1.5 times greater in the large body than in the small body phantom. RMS errors of the calculated volume fractions of red marrow within 2 × 2 segmented subregions of the ROIs were 1.6–1.9 times greater than for no segmentation, and RMS errors for 3 × 3 segmented subregions were 2.3–2.7 times greater than those for no segmentation. Increasing the dose by a factor of 2 reduced the RMS errors of all constituent volume fractions by an average factor of 1.40 ± 0.29 for all segmentation schemes and body phantom sizes; increasing the dose by a factor of 4 reduced those RMS errors by an average factor of 1.71 ± 0.25. Results

  4. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    Directory of Open Access Journals (Sweden)

    Welling JD

    2012-04-01

    Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

  5. From Leflunomide to Teriflunomide: Drug development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2016-12-08

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, the increased number of approved substances and the possibility of an oral availability of some immunomodulators improve the therapeutic repertory and increase patient satisfaction and compliance. Teriflunomide is indicated as first line oral disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Its immunosuppressive capacity results from an inhibition of de novo pyrimidine synthesis in rapidly proliferating lymphocytes. While Teriflunomide has been approved for the treatment of RRMS only since 2012, there is substantial therapeutic experience with its prodrug Leflunomide used in the treatment of rheumatoid arthritis (RA). In MS, a daily dose of 14 mg Teriflunomide reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo while it provides a reasonable safety profile. This review presents an overview on oral immunosuppressants used in the treatment of MS. With an emphasis on Teriflunomide it summarizes discovery, mechanism of action and clinical effectiveness in phase II and III trials as well as important aspects for treating physicians.

  6. A new side effect of immunosuppression: high incidence of hearing impairment after liver transplantation.

    Science.gov (United States)

    Rifai, Kinan; Kirchner, Gabriele I; Bahr, Matthias J; Cantz, Tobias; Rosenau, Jens; Nashan, Björn; Klempnauer, Jürgen L; Manns, Michael P; Strassburg, Christian P

    2006-03-01

    Little is known about hearing impairment in patients after organ transplantation. We conducted a single-center study to evaluate hearing impairment in patients after orthotopic liver transplantation (OLT). A questionnaire was sent to 695 adult patients after OLT to assess characteristics and course of auditory impairment. Risk factors such as ototoxic drugs were taken into consideration. Clinical follow-up, including immunosuppressive therapy, was analyzed in detail. The questionnaire was completed by 521 patients (75%). Hearing impairment was reported by 184 patients (35%). A total of 43 patients (8%) suffered from hearing abnormalities prior to OLT. The remaining 141 patients (27%) developed hearing impairment after transplantation. Main problems were hearing loss (52%), tinnitus (38%), and otalgia (30%). There was no association of post-OLT hearing disorders with age or known risk factors. In 43% of patients, onset of hearing impairment was within 2 yr post-OLT. Hearing loss was positively associated with tacrolimus immunosuppression in univariate (P Patients using a hearing aid received tacrolimus more frequently than cyclosporine (P hearing impairment is frequent in patients after OLT and contributes to post-OLT morbidity. Calcineurin inhibitor-related neurotoxicity appears as a possible mechanism. Further prospective investigations with objective hearing tests are necessary to confirm these results and to evaluate the role of immunosuppression.

  7. 重型再生障碍性贫血免疫抑制治疗后恶性克隆造血临床分析%Clinical analysis on malignant clonal hematopoiesis in severe aplastic anemia patients with immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    崔宁博; 付蓉; 瞿文; 阮二宝; 王晓明; 王国锦; 吴玉红; 刘鸿; 关晶

    2015-01-01

    目的 探讨重型再生障碍性贫血(SAA)患者联合免疫抑制治疗(IST)后出现7号染色体缺失(-7)恶性克隆造血的临床特征和危险因素.方法 回顾性分析天津医科大学总医院血液科2004年10月至2012年1月IST后出现-7染色体异常的SAA患者的临床资料.结果 SAA患者IST后出现-7染色体异常的比例为4.2% (6/143),出现异常的中位时间是IST后36(12~ 75)个月.此6例患者均诊断为骨髓增生异常综合征(MDS),其中3例进展为急性髓系白血病(AML),时间分别为IST后24、45和51个月.中位随访时间42(17~84)个月,4例患者随访期间死亡,从确诊MDS到死亡中位时间是9(5 ~17)个月,3例患者死于感染,1例患者死于脑出血.6例患者临床特点包括IST后6个月治疗无效、IST联合重组人粒细胞集落刺激因子(rHu-GCSF)治疗后1个月单核细胞百分比升高、IST联合rHu-GCSF后3个月处于粒细胞缺乏状态.结论 SAA患者经IST后粒系反应不良提示恶性克隆性造血存在,且预后差.%Objective To investigate the clinical characteristics and risk factors of monosomy 7 malignant clonal evolution in patients with severe aplastic anemia (SAA) treated with combined immunosuppressive therapy(IST).Methods The clinical data of SAA patients treated with IST who had monosomy 7 malignant clonal evolution from October 2004 to January 2012 were analyzed respectively.Results Six patients (4.2%) had monosomy 7 clonal evolutions.The median time to monosomy 7 was 36 (12-75) months after IST.All 6 patients were diagnosed myelodysplastic syndromes (MDS).Among them,3 patients transformed to acute myeloid leukemia following MDS.The time was 24,45 and 51 months after IST.The median following time was 42 (17-84) months.Four patients died during the following time.The median time from MDS to death was 9 (5-17) months.Among them,three patients died with infection,one died with cerebral hemorrhage.Six patients had the clinical characteristics

  8. The impact of immunosuppressive therapy on genetic instabilities of bone marrow hematopoietic cells in patients with aplastic anemia%免疫抑制治疗对再生障碍性贫血患者骨髓细胞遗传不稳定性的影响

    Institute of Scientific and Technical Information of China (English)

    张丽红; 刘强; 储榆林; 张凤奎; 王慧君; 张莉; 周康; 杨栋林; 阎璋松; 李洪强; 刘庆国; 齐军元

    2008-01-01

    Objective To investigate the impact of immunosuppressive therapy(IST) on genetic in-stabilities of bone marrow hematopoietic cells (BMHCs) in patients with aplastic anemia(AA). Methods Comet assay as used to detect genetic instabilities of hematopoietic ceils from patients, and the percent of DNA in comet tail (TDNA), tail length(TL), tail moment(TM), olive tail moment(OTM) and the rate of comet cells were measured. BMHCs from AA patients were examined with comet assay before and after IST, and the results were compared with those from controls. Results Comet parameters from 91 AA patients in-cluding TDNA, TL, TM, OTM comet cell percentage were (5.0 ± 4.0) %, 11.3 ± 7.2, 1.7 ± 2.0, 1.5 ± 1.4, (16.8 ± 13.7)%, respectively, which were significandy higher than those from control group (P 0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4±3.6)%, 10.4 ± 7.5, 1.4 ± 1.6, 1.3 ± 1.4 and (20.2 ± 21.2) %, respectively at 3 months after [ST in 53 SAA pa-tients and were (3.7 ± 3.3) %, 10.0 ± 7.2, 1.2 ± 1.8, 1.1 ± 1.3 and (18.5 ± 19.0) % respectively at 6 months after IST in 30 SAA patients, being no statistical difference from those of 58 SAA patients before IST (P values were all > 0. 05). Conclusion B MHCs of AA had inherent genetic instabilities which were not increased by recent IST. It indicated that there was no correlation between LST and the development of clonal hematologic disorders in AA.%目的 研究强烈免疫抑制治疗(IST)对再生障碍性贫血(AA)患者骨髓细胞遗传不稳定性的影响.方法 采用彗星试验检测患者骨髓细胞遗传不稳定性,以彗星尾部DNA(TDNA)百分比、尾长(TL)、尾矩(TM)、Olive尾矩(OTM)和彗星细胞率作为分析参数,分别检测IST前后AA患者骨髓细胞,并与对照组结果比较.结果 91例初治从患者TDNA百分比、TL、TM、OTM、彗星细胞率分别为(5.0±4.0)%、11.3±7.2、1.7±2.0、1.5±1.4、(16.8±13.7)%,明显高于对照组(P值均0.05),二组患

  9. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation

    DEFF Research Database (Denmark)

    McAlister, V C; Haddad, E; Renouf, E

    2006-01-01

    A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were...

  10. Safety and efficacy of dual therapy with GSK233705 and salmeterol versus monotherapy with salmeterol, tiotropium, or placebo in a crossover pilot study in partially reversible COPD patients

    Directory of Open Access Journals (Sweden)

    Brooks J

    2012-03-01

    across the treatment groups, with headache the most frequently reported treatment-related AE reported by one subject receiving each of GSK233705 20 µg + salmeterol, tiotropium, and placebo. No significant differences were seen in vital signs, ECGs, or laboratory parameters between the groups.Conclusion: The addition of GSK233705 to salmeterol in partially reversible COPD patients resulted in greater bronchodilation than salmeterol or tiotropium alone and was well tolerated.Keywords: COPD, bronchodilation, dual therapy, LAMA, LABA

  11. Effects of dexamethasone immunosuppression on turkey clostridial dermatitis.

    Science.gov (United States)

    Thachil, Anil J; Shaw, Daniel P; Nagaraja, Kakambi V

    2014-09-01

    Clostridia represents a group of anaerobic spore-forming bacteria ubiquitous in the poultry environment. They are widely distributed in soil and survive for many years as highly resistant, inactive spores. They enter the body through wounds and contaminated feed as active bacteria or spores. Multiplication of clostridial bacteria occurs only in the absence of oxygen or in environments with very low concentrations of oxygen. During active multiplication, the clostridial organisms produce several toxins that are responsible for most of the clinical signs seen in clostridial diseases. Immunosuppression is a problem for the poultry industry. In modern, intensive poultry-rearing conditions, stress due to high population densities pose a considerable challenge for the immune system, and infectious agents can exploit this situation to cause disease. Immunosuppression may predispose turkeys to clostridial infection, resulting in clostridial dermatitis and mortality. The purpose of this study was to determine whether immunosuppression predisposes turkeys to clostridial infection and causes clostridial dermatitis. We immunosuppressed 10-wk-old turkey poults with dexamethasone. The birds immunosuppressed and not immunosuppressed were then challenged with Clostridium perfringens, Clostridium septicum, or both and examined for the development of clostridial dermatitis. The dexamethasone-treated birds were found to be more susceptible to C. peifingens/C. septicum challenge and developed clostridial dermatitis than the no-dexamethasone-treated birds through the subcutaneous route. However, oral inoculation of the same agents did not cause any dermatitis lesions in either of the groups.

  12. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    Science.gov (United States)

    Chocair, P; Duley, J; Simmonds, H A; Cameron, J S; Ianhez, L; Arap, S; Sabbaga, E

    1993-07-10

    Early rejection can still complicate renal transplantation even with cyclosporin. We added low-dose allopurinol (25 mg on alternative days) to "triple" immunosuppression with cyclosporin, prednisolone, and azathioprine for twelve recipients of cadaver renal grafts. The controls were fifteen patients on triple therapy alone. Only one rejection episode occurred among the allopurinol-treated patients, whereas eleven controls had rejections (seven with more than one episode). Allopurinol may be toxic when combined with azathioprine, yet the bone marrow tolerated the new regimen well. As expected, reduction of the azathioprine dose was necessary in the treated group.

  13. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients.

    Science.gov (United States)

    Penninga, Luit; Penninga, Elisabeth I; Møller, Christian H; Iversen, Martin; Steinbrüchel, Daniel A; Gluud, Christian

    2013-05-31

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without causing adverse effects. To assess the benefits and harms of tacrolimus versus cyclosporin for primary immunosuppression in lung transplant recipients. We searched the Cochrane Renal Group's Specialised Register to 10 April 2013 through contact with the Trials Search Co-ordinator using search terms relevant to this review. We also searched Science Citation Index Expanded and the Transplant Library to 20 April 2013. We included all randomised controlled trials (RCT) that compared any dose and duration of administration of tacrolimus versus cyclosporin as primary immunosuppressive treatment in lung transplant recipients. Our selection criteria required that all included patients received the same additional immunosuppressive therapy within each study. Three authors extracted data. For dichotomous data we used risk ratio (RR) and used mean difference (MD) for continuous data, each with 95% confidence intervals (CI). Methodological components of the included studies were used to assess risk of systematic errors (bias). Trial sequential analysis was used to assess risk of random errors (play of chance). We included three studies that enrolled a total of 413 adult patients that compared tacrolimus with microemulsion or oral solution cyclosporin. All studies were found to be at high risk of bias. Tacrolimus seemed to be significantly superior to cyclosporin regarding the incidence of bronchiolitis obliterans syndrome (RR 0.46, 95% CI 0.29 to 0.74), lymphocytic bronchitis score (MD -0.60, 95% CI -1.04 to -0.16), treatment withdrawal (RR 0.27, 95% CI 0.16 to 0.46), and arterial hypertension (RR 0.67, 95% CI 0.50 to 0.89). However, the finding for arterial hypertension was not

  14. Dual diagnosis

    OpenAIRE

    2013-01-01

    Dual diagnosis denotes intertwining of intellectual disabilities with mental disorders. With the help of systematic examination of literature, intellectual disabilities are determined (they are characterized by subaverage intellectual activity and difficulties in adaptive skills), along side mental disorders. Their influence is seen in changes of thinking, perception, emotionality, behaviour and cognition. Mental disorders often occur with people with intellectual disabilities (data differs f...

  15. Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent  Clostridium difficile Infection

    Directory of Open Access Journals (Sweden)

    Hadeel Zainah

    2012-01-01

    Full Text Available We report a case of ulcerative colitis (UC and recurrent Clostridium difficile infection (CDI where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.

  16. Preservation of vaccine-induced long-term B cell memory and the effects of immunosuppressive treatment

    OpenAIRE

    Ingelman-Sundberg, Hanna M.

    2015-01-01

    Immune memory after vaccination is largely dependent on the combination of antibody production from long-lived plasma cells, and a supporting pool of antigen-primed memory B cells. It has been observed that individuals with certain immunosuppressive conditions or treatments have a weakened B cell memory, but the mechanisms behind remain elusive. The aim of this thesis was to evaluate B cell immunity in healthy children, and how HIV-1 infection, antineoplastic therapy, and rheum...

  17. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

  18. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Institute of Scientific and Technical Information of China (English)

    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective:To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).Data Sources:We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators).The following terms were used:"inflammatory bowel disease (IBD)" OR "Cmhn's disease" OR "ulcerative colitis"AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators."Study Selection:The inclusion criteria of articles were that the studies:(1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical,radiographic,endoscopic,and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping,15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy,antibiotics only,mesalazine only,biological agent only such as infliximab,adalimumab,certolizumab or natalizumab or within 3 months of stopping one of these agents).The exclusion criteria of articles were that the studies:(1) History of hepatitis B virus (HBV),influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV,influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g.chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.Results:Patients treated with immunomodulators were associated with lower response rates to vaccination

  19. Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: its application to targeted sonodynamic therapy.

    Science.gov (United States)

    Ninomiya, Kazuaki; Noda, Kyohei; Ogino, Chiaki; Kuroda, Shun-ichi; Shimizu, Nobuaki

    2014-01-01

    The present study demonstrated the enhanced hydroxyl (OH) radical generation by combined use of dual-frequency (0.5 MHz and 1 MHz) ultrasound (US) and titanium dioxide (TiO2) nanoparticles (NPs) as sonocatalyst. The OH radical generation became the maximum, when 0.5 MHz US was irradiated at an intensity of 0.8 W/cm(2) and 1 MHz US was irradiated at intensities at 0.4 W/cm(2) in the presence of TiO2 NPs under the examined conditions. After incorporation of TiO2 NPs modified with targeting protein pre-S1/S2, HepG2 cancer cells were subjected to the dual-frequency US at optimum irradiation intensities ("targeted-TiO2/dual-US treatment"). Growth of the HepG2 cells was reduced by 46% compared with the control condition after irradiation of dual-frequency US for 60s with TiO2 NPs incorporation. In contrast, HepG2 cell growth was almost the same as that in the control condition when cells were irradiated with either 0.5 MHz or 1 MHz ultrasound alone without TiO2 NP incorporation. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience

    Institute of Scientific and Technical Information of China (English)

    Jian Zhou; Yi-Feng He; Yu-Qi Wang; Zhao-You Tang; Jia Fan; Zheng Wang; Zhi-Quan Wu; Shuang-Jian Qiu; Xiao-Wu Huang; Yao Yu; Jian Sun; Yong-Sheng Xiao

    2006-01-01

    AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune(R), rapamycin) in a consecutive cohort of 248 liver allograft recipients.METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT.RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT.Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable.CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

  1. Skin cancer development in mice exposed chronically to immunosuppressive agents.

    Science.gov (United States)

    Daynes, R A; Harris, C C; Connor, R J; Eichwald, E J

    1979-04-01

    Inbred female C3Hf/HeN, murine mammary tumor virus-negative mice exposed to either UV light or benzo[a]pyrene (BP), were subjected to four different chronic immunosuppressive regimens to determine their effect on skin cancer development. The immunosuppressive agents were cyclophosphamide, methotrexate, cortisone, and heterologous antilymphocyte globulin. Because of an unexpectedly high morbidity and mortality of mice exposed to chronic immunosuppressive measures, the dosages were kept at a level that permitted them to survive but did not prolong allogeneic skin graft survival and lower antibody titers, nor did this level diminish proliferative responses of lymphocytes to mitogens or allogeneic lymphocytes. Nevertheless, the latency periods (time interval between beginning of medication and appearance of skin tumors) of tumors in mice exposed to immunosuppressant measures were significantly shortened in several groups of mice exposed to UV and subjected to cyclophosphamide, cortisone, or antilymphocyte globulin and mice exposed to BP and subjected to cortisone acetate. In 3 groups, spindle cell tumors (fibrosarcomas) shifted to squamous cell carcinomas. A suppressed immune function would not be regarded as the mechanism for the observed responses because immunosuppression was not detected in the experimental mice.

  2. The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients.

    Science.gov (United States)

    Bernat-García, J; Morales Suárez-Varela, M; Vilata-Corell, J J; Marquina-Vila, A; Pallardo, L; Crespo, J

    2014-12-01

    Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs. Copyright © 2014. Published by Elsevier Espana.

  3. Relationship between mycophenolate mofetil dose and mycophenolate acid exposure in renal allograft recipients during maintenance immunosuppressive therapy%肾移植受者免疫抑制维持治疗期霉酚酸酯剂量与霉酚酸暴露的关系

    Institute of Scientific and Technical Information of China (English)

    安会敏; 周佩军; 徐达; 王祥慧; 邵琨

    2012-01-01

    Objective To investigate the level of mycophenolate acid ( MPA) exposure in renal allograft recipients receiving mycophenolate mofetil ( MMF) as maintenance immunosuppressive therapy. Methods Sixty renal allograft recipients were treated with cyclosporine A (CsA), MMF and prednisone (Pred), peripheral vein blood samples were obtained 0. 5 h, 2 h and 4 h after administration of MMF, the plasma concentrations of MPA were measured by enzyme-multiplied immunoassay technique. The values of area under the curve ( AUC) of plasma MPA concentration ( MPA AUC) of the renal allograft recipients were calculated by the simplified formula of limited sampling strategy. All recipients were divided into low dose MMF group ( MMF 1.5 g/d, n = 13) according to doses of oral administration of MMF. Besides, all recipients were divided into low exposure to MPA group (MPA AUC 60 mg·h·L-1) according to values of MPA AUC. Results The mean MPA AUC of 60 renal transplant recipients was (59. 83 ± 19.42) mg·h·L-1. There were 3 cases (5.0%) in low exposure to MPA group, 31 cases (51.7%) in target exposure to MPA group and 26 cases (43. 3%) in high exposure to MPA group. The mean doses of CsA in low exposure to MPA group, target exposure to MPA group and high exposure to MPA group were (166.67 ±14.43) mg/d, (137. 10 ±41.27) mg/d and (128. 85 ±37. 88) mg/d respectively, exhibiting a decreasing tendency, while there was no significant difference among groups (P >0. 05). Conclusion Under the condition of MMF dose adjustment based on clinical events without MPA AUC monitoring, MPA tends to be highly exposed in renal allograft recipients. There are significant inter-individual variations in MPA pharmacokinetics, and it is necessary to perform MMF monitoring in treatment for renal allograft recipients.%目的 观察服用霉酚酸酯(MMF)的肾移植受者在免疫抑制维持治疗期霉酚酸(MPA)的暴露水平.方法 60例肾移植受者均采用环孢素A(CsA)、MMF和强的松(Pred)三

  4. 比较不同重组人TPO方案联合免疫抑制治疗对重型再生障碍性贫血近期疗效的影响%Comparison of efficacy and safety of two different dose of recombinant human thrombopoietin regimens in severe aplastic anemia patients with immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    周康; 李洋; 李建平; 樊慧慧; 张莉; 井丽萍; 彭广新; 叶蕾; 李园

    2016-01-01

    Objective To compare the short-term therapeutic effect of different regimens combining recombinant human thrombopoietin (rhTPO) with immunosuppressive therapy (IST) applied in severe aplastic anemia (SAA).Methods The clinical data of newly diagnosed adult SAA patients treated with first-line IST,including 18 patients with rhTPO daily and 43 patients with rhTPO every other day,was analyzed retrospectively.Results There was no significant difference between the basic clinical characteristics of the patients classified in different groups.The therapeutic effect was assessed 3 months and 6 months after IST.The statistical data revealed that the overall responses (OR) were not significantly different in daily group and every other day group (3 months:50.0% vs 51.2%,P=0.934;6 months:77.8% vs 69.8%,P=0.525),while the good hematological response (CR+GPR) in SAA treated with rhTPO daily was significantly higher than that of patients treated with rhTPO every other day at 3 month after IST (38.9% vs 9.3%,P=0.011).RBC transfusion independence were not significantly different between the two groups after 4 weeks as well as 8 weeks treatment(4 weeks:22.2% vs 18.6%,P=0.736;8 weeks:55.6% vs 46.5%,P=0.519),while platelet transfusion independence in rhTPO daily treated group was significantly higher than that in every other day group (88.9% vs 48.8%,P=0.003).In addition,there were no more adverse events observed in rhTPO daily group.Conclusions It' s more effective to promote hematopoietic recovery and reduce platelet transfusion dependence when rhTPO was daily used other than used every other day.%目的 比较不同重组人TPO(rhTPO)方案联合免疫抑制剂治疗重型再生障碍性贫血(SAA)的近期疗效.方法 回顾性分析接受一线免疫抑制治疗(IST)成人SAA初诊患者资料,对比分析18例IST联合rhTPO每日1次(连续组)与43例IST联合rhTPO隔日1次(间日组)患者的疗效差异.结果 两组患者在IST前基础临床特

  5. Impact of recombinant human thrombopoietin (rhTPO) on short-term response of immunosuppressive therapy in patients with newly diagnosed acquired severe aplastic anemia%重组人血小板生成素对重型再生障碍性贫血免疫抑制治疗近期疗效的影响

    Institute of Scientific and Technical Information of China (English)

    张莉; 杨文睿; 叶蕾; 周康; 井丽萍; 李洋; 李园; 李建平; 彭广新

    2015-01-01

    Objective To evaluate the impact of recombinant human thrombopoietin (rhTPO) on short-term response of immunosuppressive therapy (IST) in patients with newly diagnosed acquired severe aplastic anemia (SAA).Methods The clinical data of forty adult acquired SAA patients,who treated with IST combined with rhTPO,were retrospective analyzed and the hematologic recovery were compared with patients by the IST alone during the same period.The factors affecting the short-term response were also analyzed.Results At 3 months after IST,both the total response rate and CR+GPR rate in rhTPO group were much higher than those in control group (75.0% vs 50.0%,P=0.022; and 17.5% vs 2.5%,P=0.025).At 6 months after IST,there was no difference of total hematologic response rate in rhTPO group and control group (77.5% vs 57.5%,P=0.058),while the CR+GPR rate was still higher in rhTPO group (45.0% vs 22.5%,P=0.033).The median time of platelet transfusion independence was much shorter in rhTPO group [33 (0-90) vs 53 (0-75) d,P=0.019].Patients in rhTPO group needed less platelets transfusion support.The median platelet count in rhTPO group was 29(4-95)× 109/L at 3 months after IST,which was much higher than that in control group [29 (4-95) × 109/L,P=0.006].There was no significant difference regarding overall survival between the two groups (100.0% vs 91.0%,P=0.276).Conclusion rhTPO is effective in promoting platelet recovery and improving the hematopoietic response for SAA patients with IST.%目的 评价重组人血小板生成素(rhTPO)对重型再生障碍性贫血(SAA)免疫抑制治疗(IST)近期疗效的影响.方法 回顾性分析IST联合rhTPO治疗40例成人SAA患者,以同期单用标准IST方案的患者为对照组,比较两组患者血液学反应及血小板恢复情况,并分析影响近期疗效的相关因素.结果 IST后3个月,rhTPO组患者血液学反应率及良好血液学反应率均明显高于对照组(75.0%对50.0%,P=0.025;17.5%对2

  6. Immunosuppression in pregnant women with systemic lupus erythematosus.

    Science.gov (United States)

    Ponticelli, Claudio; Moroni, Gabriella

    2015-05-01

    Most pregnancies are successful in women with systemic lupus erythematosus, particularly if the disease is quiescent and there are no signs of active nephritis. There is no major impact of immunosuppression on maternal outcome. However, high doses of cyclosporine and glucocorticoids are used which may favor development of hypertension or preeclampsia. Some immunosuppressive drugs may exert toxic effects on the fetus. Glucocorticoids may cause small birth weight, and azathioprine and calcineurin inhibitors may be associated with lower birth weight, gestational age and prematurity. Cyclophosphamide may cause fetal malformation when given in the first trimester. Mycophenolate and leflunomide are teratogenic drugs and should be withdrawn before conception in case of programmed pregnancy or should be rapidly discontinued in case of unexpected pregnancy. Option counseling for pregnancy and correct use of immunosuppressive drugs are prerequisites for a successful pregnancy in women with lupus.

  7. New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps.

    Science.gov (United States)

    Mi, Jia-Ning; Han, Yuwei; Xu, Yingqiong; Kou, Junping; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-12-14

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps.

  8. In vitro study of immunosuppressive effect of apoptotic cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-jin; ZHENG Shu-sen

    2005-01-01

    Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from lipopolysaccharide (LPS)-stimulated macrophages, in which the secretion of immunosuppressive cytokines such as interleukin-10 (IL-10) is increased while the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β) and leukin-8 (IL-8) are suppressed. In this paper, we first present evidence that phagocytosed apoptotic cells regulate cytokine secretion of LPS-stimulated macrophages, but also inhibit the activation of T lymphocytes stimulated by ConA. These data suggest that apoptotic cells can alter the biological behavior of macrophages which gain immunosuppressive property.

  9. QCD Dual

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2009-01-01

    We uncover a novel solution of the 't Hooft anomaly matching conditions for QCD. Interestingly in the perturbative regime the new gauge theory, if interpreted as a possible QCD dual, predicts the critical number of flavors above which QCD in the nonperturbative regime, develops an infrared stable...... fixed point. Remarkably this value is identical to the maximum bound predicted in the nonpertubative regime via the all-orders conjectured beta function for nonsupersymmetric gauge theories.......We uncover a novel solution of the 't Hooft anomaly matching conditions for QCD. Interestingly in the perturbative regime the new gauge theory, if interpreted as a possible QCD dual, predicts the critical number of flavors above which QCD in the nonperturbative regime, develops an infrared stable...

  10. Down-regulated NOD2 by immunosuppressants in peripheral blood cells in patients with SLE reduces the muramyl dipeptide-induced IL-10 production.

    Directory of Open Access Journals (Sweden)

    Shui-Lian Yu

    Full Text Available BACKGROUND: Pattern recognition receptors (PRRs such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs in systemic lupus erythematosus (SLE patients, for playing immunopathological roles. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the expression and function of the PRR nucleotide-binding oligomerization domain (NOD2 in SLE. NOD2 expression in T, B lymphocytes, monocytes, myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs was assessed in SLE patients and healthy controls (HCs using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon NOD2 agonist muramyl dipeptide (MDP stimulation was assessed using Cytometric Bead Array. Over-expression of NOD2 in monocytes was observed in immunosuppressant naïve SLE patients, and was positively associated with longer disease duration. Immunosuppressive therapy was an independent explanatory variable for downregulating NOD2 expression in CD8+ T, monocytes, mDCs and pDCs. Ex vivo basal productions of cytokines (IL-6, IL-8 and IL-10 were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (% of cytokines (IL-1β from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (% of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs. CONCLUSIONS/SIGNIFICANCE: Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the

  11. [Low cyclosporin levels induced by the brief use of rifampicin; immunosuppression may fail for several weeks].

    Science.gov (United States)

    Valk-Swinkels, Corinne G H; Alidjan, Fazil; Rommers, Mirjam K; Bakker, René C; Swen, Jesse J; van 't Veer, Nils E

    2013-01-01

    Cyclosporin is an immunosuppressive agent with a wide range of therapeutic uses. In transplant patients, it is used for the prevention of rejection and graft-versus-host reactions. The metabolism and bioavailability of cyclosporin can be significantly and persistently influenced through induction of CYP3A4 caused by the concomitant use of rifampicin. However, awareness of the need for the timely and frequent monitoring of cyclosporin levels during and especially after treatment with rifampicin has not fully been addressed. Here, we describe 3 patient cases concerning significant episodes of sub-therapeutic cyclosporin levels after short-term rifampicin therapy. Rifampicin was administered for three to five days and decreased cyclosporin levels were observed ± 7 days after the initiation of rifampicin, and continued during the following weeks even after the cessation of rifampicin therapy. Cyclosporin dosage-adjustments were made based on the cyclosporin blood levels and all 3 patients showed good therapeutic and clinical responses.

  12. Relationship between immunosuppressive medications adherence and quality of life and some patient factors in renal transplant patients in Iran.

    Science.gov (United States)

    Shabany Hamedan, Maryam; Mohamad Aliha, Jaleh

    2014-04-16

    About organ transplant, immunosuppressive medications adherence is a critical issue, because non-adherence to these medications causes rejection, reduces quality of life and increases treatment cost and mortality rate. Among these, the quality of life is deemed very important to evaluate treatment result and also it can be useful for discovering non adherence. The aim this study was to assess the relationship between medication adherence and quality of life and some patient factors in renal transplant patients. The study was a descriptive-correlational design and was done on renal transplant patients over 18 who had undergone surgery for over 3 months, and were inclined to participate. Sample size was 230 people and sampling was convenience. Quality of life questionnaire in renal transplant patients and Immunosuppressant Therapy Adherence Scale were filled by patients and the data was analyzed by SPSS15 software. It showed that the mean score of quality of life in renal transplant patients was 21.65±4.03 and 57.8% of them did not adhere to immunosuppressive medications. Results of correlation between scores of immunosuppressive medication adherence and Quality of life showed that there were significant correlation in 3 dimensions of 4: health performance (p ≤ 0.0001 & rETA=0.23), social-economic (p=0.001 & rETA=0.15), psychological-spiritual (p=0.011 & rETA=0.15), also logistic test showed significant relationship between immunosuppressive medication adherence and number of transplantation (?=1.04, p= 0.048). According to the results, health care providers i.e. nurses must note to medication adherence as a health enhancement factor while treating and educating to these patients.

  13. Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

    Science.gov (United States)

    Alter, Mareike; Satzger, Imke; Schrem, Harald; Kaltenborn, Alexander; Kapp, Alexander; Gutzmer, Ralf

    2014-06-01

    Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley

  14. Sequence and timing of immunosuppressants-thymectomy combination therapy in patients with myasthenia gravis%免疫抑制-胸腺切除联合治疗顺序和手术时机对重症肌无力结局的影响

    Institute of Scientific and Technical Information of China (English)

    刘欣欣; 李然; 于磊; 景筠

    2015-01-01

    Objective Following the prognosis of patients with myasthenia gravis(MG) who received both immunosuppressants and thymectomy, to determine whether the sequence and timing of treatment have influences on outcomes of MG and also to select significant predictors of prognosis.Methods It was a retrospective study which reviewed 105 patients with MG who underwent thymectomy and immunosuppressants between Januay, 2000 and December, 2013.All patients were divided into two subgroups based on their order of treatment.Thirty two patients were called as immunosuppressants-first group, and 73 patients were called as thymectomy-first group.The ratios of ideal status of two groups were compared with use of the ChiSquare test.Predictors of ideal status were analyzed by logistic regression.Results (1) After 1 year, 2 years and 5 years of intervention, the proportion of ideal status was significantly higher in the thymectomy-first group than that in the immunosuppressants-first group[(33%-50%) vs.(10%-20%), P <0.05].For oMG patients, after 1 year, 2 years and 5 years of treatment, thymectomy-first group had a higher ideal status rates than immunosuppressants-first group[(25%-50%) vs.(11%-18%)].But no significant difference was noted in the rates of ideal status at each follow-up time point.(2)Multivariate logistic regression analysis showed that sequence of treatment (OR =0.154, 95 % CI: 0.046-0.518, P =0.002) and symptom-thymectomy interval(OR =0.903,95 % CI: 0.835-0.976, P =0.010) were the significant predictors of ideal status.Conclusion Thymectomy prior to immunosuppressants is associated with relatively good prognosis.It is suggested that patients with gMG, or adult patients with oMG who are resistant to drug, will be better to undergo thymecotomy as early as possible.%目的 研究免疫抑制-胸腺切除联合治疗策略对重症肌无力(MG)结局的影响.方法 回顾性研究2000年1月至2013年12月免疫抑制-胸腺切除联合治疗105例,根

  15. Ischemic ''memory image'' in acute myocardial infarction of {sup 123}I-BMIPP after reperfusion therapy. A comparison with {sup 99m}Tc-pyrophosphate and {sup 201}Tl dual-isotope SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Teruhito; Miyagawa, Masao; Sugawara, Yoshifumi; Kikuchi, Takanori; Ikezoe, Junpei [Ehime Univ., Matsuyama (Japan). School of Medicine; Murase, Kenya [Osaka Univ., Suita (Japan). Medical School; Higashino, Hiroshi [Ehime Imabari Hospital (Japan)

    2002-12-01

    Ischemic ''memory image'' is a phenomenon of {sup 123}I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in which an area at risk of acute myocardial infarction (AMI), could be detected as a defect in a couple of weeks even after successful reperfusion therapy. The purpose of this study was to clarify the incidence of the ischemic ''memory image'' of {sup 123}I-BMIPP in patients with AMI by comparing {sup 99m}Tc-pyrophosphate(PYP) and {sup 201}Tl dual-isotope SPECT. Materials consisted of 14 patients with successfully reperfused AMI and 20 patients with old myocardial infarction (OMI). All AMI patients underwent PYP/Tl dual-isotope SPECT within 1 week after the onset of AMI, and BMIPP SPECT was performed within 1 week after the PYP/Tl dual-isotope SPECT. The extent and severity of the defect of BMIPP and Tl were visually scored into four grades: 0=no defect to 3=large or severe defect. These scores were compared. PYP positive AMI lesions were concordant with BMIPP defects (13/14). In AMI, both the extent and severity scores of BMIPP were higher than {sup 201}Tl (p<0.001). Differences (BMIPP-Tl) of extent and severity scores were greater in AMI than in OMI (p<0.001). In conclusion, the ischemic ''memory image'' obtained by means of the BMIPP is a common phenomenon (13/14) in AMI, and helpful in evaluating the area at risk. (author)

  16. An immunosuppressive tryptophan-derived alkaloid from Lepidagathis cristata.

    Science.gov (United States)

    Ravikanth, V; Niranjan Reddy, V L; Ramesh, P; Prabhakar Rao, T; Diwan, P V; Khar, A; Venkateswarlu, Y

    2001-12-01

    An immunosuppressive, tryptophan-derived alkaloid cristatin A (1), and two known compounds, cycloartenol and stigmasta-5,11(12)-diene-3 beta-ol, were isolated from the whole plant Lepidagathis cristata Willd. The structures of the isolates were established by interpretation of their spectral data.

  17. Immunosuppressive principles from Achillea talagonica, an endemic species of Iran

    Directory of Open Access Journals (Sweden)

    S Saeidnia

    2009-03-01

    Full Text Available ABSTRACT Background and the purpose of study: Achillea talagonica Boiss. (Asteraceae grows in the western and central parts of Iran. This plant has long been used in traditional medicine as an anti-inflammatory agent for treatment of rheumatic pain. Previously, the immunosuppressive activity of the aqueous extract of this endemic plant in experimental animals was reported. In this research, isolation of the main immunologically active components of A. talagonica, which were effective on humoral immune responses in BALB/c mice is elucidated. Methods: In order to find the main immunosuppressive components of A. talagonica, methanol and methanol-water (80% and 50% v:v extracts were injected to BALB/c mice and the hemagglutinating antibody titer was assayed after immunization with SRBC (sheep red blood cells. Guided by this assay, active principles were separated by chromatographic methods. Results: Isolated compounds were identified as caffeic acid 9-O-glucoside (1, quercetin (2, luteolin (3, 3'-methoxy luteolin (4, proline (5 and choline (6 by comparison of their spectral data with those of reported in literatures. Immunosuppressive property of choline (5 mgkg-1 was comparable to those of prednisolone (10 mgkg-1; although, quercetin (20 mgkg-1 and caffeoyl glucoside (20 mgkg-1 decreased anti-SRBC titer in comparison with control groups. Major conclusion: Immunosuppressive effects of A. talagonica are due to some components belonging to betaine, flavonol and phenoilc esters.

  18. The role of cytokines in ultraviolet-B induced immunosuppression

    NARCIS (Netherlands)

    Boonstra, A.; Savelkoul, H.F.J.

    1997-01-01

    Summary : Cytokines play an important role in the mechanisms resulting in ultraviolet B-induced immunosuppression. They play a crucial role in the induction of local as well as systemic immunomodulatory events. Ultraviolet B irradiation directly induces the release of cytokines in the epidermis, res

  19. Survival predictors in paraquat intoxification and role of immunosuppression

    Directory of Open Access Journals (Sweden)

    Keng-Hee Koh

    2014-01-01

    In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4% compared to historical control (30 out of 52 patients (57.7% (p = 0.885 in those with eGFR > 50 ml/min/1.73 m2 or WBC 11,000/μL.

  20. SEPARATON AND IDENTIFICATION OF IMMUNOSUPPRESSIVE FACTORS IN HUMAN SEMEN

    Institute of Scientific and Technical Information of China (English)

    CAOHui-Bao; WANGyi-Fei; JIANGYu

    1989-01-01

    The main function of immunosuppressive factors ( IFs ) in seminal plasma ( SP ) is the inhibition of immune response in genital tracts, thus the iso- and/ or autoimmune response to the spermatozoa and embryo are evaded. Studies on IFs in SP is thus important

  1. Neuromyelitis optica relapses: Race and rate, immunosuppression and impairment.

    Science.gov (United States)

    Tackley, George; O'Brien, Fanny; Rocha, João; Woodhall, Mark; Waters, Patrick; Chandratre, Saleel; Halfpenny, Christopher; Hemingway, Cheryl; Wassmer, Evangeline; Wasiewski, Warren; Leite, Maria Isabel; Palace, Jacqueline

    2016-05-01

    Neuromyelitis optica (NMO) is a rare antibody-mediated CNS disease characterised by disabling relapses leading to high morbidity and mortality. Understanding relapse activity and severity is important for treatment decisions and clinical trial design. We assessed (1) whether clinical and demographic factors associate with different relapse rates and (2) the relative impact of immunosuppressive treatments on relapse rates and on attack-related residual disability. Clinical, demographic and treatment data were prospectively collected from 79 consecutive aquaporin 4 antibody positive patients seen in the nationally commissioned Oxford NMO service. The influence of clinical features on annualised relapse rates (using multiple regression) and the effect of immunosuppression on relapse-associated residual disability for transverse myelitis and optic neuritis attacks (using a mixed effect model) were analysed. The mean annualised relapse rate was 0.93. Relapse rates were significantly higher in Afro-Caribbeans, children and in those of shorter disease duration. Relapse rates reduced on treatment (from 0.87 to 0.42). Delay to first treatment did not influence eventual on-treatment relapse rate. Immunosuppressive treatment significantly reduced the residual disability from ON (p<0.01), and TM (p=0.029) attacks. Relapse rates in NMO are influenced by multiple factors, including age, ethnicity and disease duration. Current immunosuppressive treatments reduce but do not abolish relapses, however, they appear to additionally lessen the chronic disabling effect of a relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effects of flavonoids on anti-carcinogenesis and immunosuppression

    NARCIS (Netherlands)

    Steerenberg PA; Garssen J; Beems RB; Dortant PM; Kranen HJ van; Kreyl CF van; Bueno de Mesquita HB; Gruyl FR de; Vos JG; Loveren H van; LPI; LEO; CCM; AZU/Dermatologie

    1998-01-01

    In this study flavonoid-rich diets and tea extracts were investigated. These diets were studied for their putative protective effect on UV induced skin tumors and tumors in the small intestine and colon. Moreover , the same diets were studied in UV induced immunosuppression. The results show that

  3. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

    2013-01-01

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

  4. Clinical Observation of Treating 62 Patients with Severe Aplastic Anemia Failing in Immunosuppressive Therapy by Integrative Medicine%中西医结合治疗62例免疫抑制治疗无效的重型再生障碍性贫血临床观察

    Institute of Scientific and Technical Information of China (English)

    苏尔云; 方玉华; 陈辉树

    2012-01-01

    目的 探讨对免疫抑制治疗(IST)无效的重型再生障碍性贫血(SAA)的治疗方法.方法 用中西医结合治疗IST无效的SAA 62例.将治疗过程分3期:危重期用羚羊乙癸汤(羚羊角粉1.2 g 黄连6 g焦栀子12 g 生地30 g 白茅根50 g 黄柏9 g 丹皮12 g 阿胶9 g 红枣30 g 炙甘草6 g等)与二至补髓汤(女贞子120 g 旱莲草100 g 制首乌24 g 枸杞子12 g 生地90 g 黄芪60 g 当归9 g 阿胶9 g金银花30 g 莲子芯12 g等)交替服用,每日1剂,煎2次分服,同时给予丙酸睾酮50 mg隔日肌肉注射,治至好转期.发热者在羚羊乙癸汤中加生石膏60 g,知母60 g,蒲公英30 g,白英30 g,白薇30 g,三叶青15 g等.好转期用鸡血藤复方治疗(肾阳虚给予鸡血藤拯阳汤:鸡血藤100 g 黄芪60 g 红参3 g 补骨脂12 g菟丝子18 g 当归12 g 仙灵脾18 g 葫芦巴6 g 制首乌24 g 女贞子30 g 旱莲草30 g 紫河车6 g等.同时给予丙酸睾酮50 mg隔日肌肉注射.肾阴虚给予鸡血藤益精汤:女贞子100 g 旱莲草100 g 生地90 g 鸡血藤30 g 菟丝子12 g 补骨脂6 g 制首乌30 g 阿胶9 g 枸杞子9 g 丹参24 g 黄芪30 g当归6 g等)每日1剂,煎2次服.治至恢复期.恢复期逐渐减药至停药随访.结果 62例患者经6~57个月的治疗,基本治愈12例(19.4%),缓解14例(22.6%),明显进步8例(12.9%),无效28例(45.2%),总有效率54.8%.初诊时体温37.6~38.5 ℃者23例,退热(38.5 ℃者20例,退热所需时间4 h~ 5天.初诊时因IST而引起的肝、肾功能异常(ALT、AST、BUN、Cr)者26例,经中西医结合治疗2个月后,25例恢复正常.结论 IST无效的SAA的治疗有其特殊性,中西医结合分期论治符合IST无效的SAA的病理生理,改善和保护骨髓造血微环境可能是治疗IST无效的SAA的关键所在.而中药的抗菌消炎作用有阻断病情恶化的趋势.%Objective To explore treatment methods for patients with severe aplastic anemia (SAA) failing in immunosuppressive therapy (IST). Methods Totally 62 SAA

  5. Immunosuppression with a combination of triptolide and cyclosporin A in rat vascularized groin flap allotransplantation.

    Science.gov (United States)

    Liu, Fei; Luo, Xusong; Lan, Shenghui; Zhang, Xianrong; Wang, Shoubao; Yang, Jun; Levin, L Scott

    2013-03-01

    Triptolide is an immunosuppressive fraction purified from a Chinese medicinal plant. In an effort to develop a new immunosuppressive strategy for vascularized composite allotransplantation, the authors investigated the effects of combined treatment with cyclosporin A and triptolide on the survival of rat groin flap allotransplants. Groin flap transplantation was performed from Brown Norway rats to Fischer 344 recipients, which were then treated with triptolide, cyclosporin A, or both. Flap biopsy specimens were harvested, stained, and submitted to histopathologic evaluation. Levels of CCR5, CCR7, CCL19, CCL21, and Foxp3 in spleen were examined by real-time polymerase chain reaction, and the percentage of CD4+CD25+ regulatory T cells was detected by flow cytometry. The mean survival time for allografts in recipients receiving triptolide and cyclosporin A was 57 ± 7.7 days compared with 20.5 ± 2.3 days for cyclosporin A alone, 23.3 ± 3.6 days for triptolide alone, and 7.8 ± 0.8 days for no treatment. Histologic examination also showed that inflammatory cell infiltration was reduced in grafts with combination treatment. Down-regulation of CCR5, CCR7, and CCL19 in the combination treatment was accompanied by increased expression of Foxp3. Flow cytometric analysis also revealed that the percentage of CD4+CD25+ regulatory T cells in the combination treatment was higher than in the monotherapy groups. Combination therapy with triptolide and cyclosporin A substantially prolonged allograft survival, which means calcineurin inhibitor-related drug-toxicity may be alleviated and treatment cost reduced. This immunosuppressive effect is mediated by inhibition of dendritic cells maturation and the expansion of regulatory T cells.

  6. Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis

    Directory of Open Access Journals (Sweden)

    Sotsiou Florentia

    2005-12-01

    Full Text Available Abstract Background Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment. Methods Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA. TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange. Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. Results Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively. In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p 1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence

  7. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

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    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  8. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

    Science.gov (United States)

    Riveiro-Barciela, M; Campos-Varela, I; Tovar, J L; Vargas, V; Simón-Talero, M; Ventura-Cots, M; Crespo, M; Bilbao, I; Castells, L

    2011-12-01

    Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

  9. Cost utility analysis of immunosuppressive regimens in adult renal transplant recipients in England and Wales

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    Muduma G

    2014-11-01

    Full Text Available Gorden Muduma,1 Jane Shaw,2 Warren M Hart,3 Abayomi Odeyemi,3 Isaac Odeyemi21Astellas Pharma Europe Limited, Chertsey, UK; 2Astellas Pharma Limited, Chertsey, UK; 3EcoStat Consulting UK Limited, London, UKBa