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Sample records for aggressive immunosuppressive therapy

  1. Immunosuppressants in cancer prevention and therapy

    PubMed Central

    Blagosklonny, Mikhail V

    2013-01-01

    Rapalogs such as rapamycin (sirolimus), everolimus, temserolimus, and deforolimus are indicated for the treatment of some malignancies. Rapamycin is the most effective cancer-preventive agent currently known, at least in mice, dramatically delaying carcinogenesis in both normal and cancer-prone murine strains. In addition, rapamycin and everolimus decrease the risk of cancer in patients receiving these drugs in the context of immunosuppressive regimens. In general, the main concern about the use of immunosuppressants in humans is an increased risk of cancer. Given that rapalogs are useful in cancer prevention and therapy, should they be viewed as immunosuppressants or immunostimulators? Or should we reconsider the role of immunity in cancer altogether? In addition to its anti-viral, anti-inflammatory, anti-angiogenic and anti-proliferative effects, rapamycin operates as a gerosuppressant, meaning that it inhibits the cellular conversion to a senescent state (the so-called geroconversion), a fundamental process involved in aging and age-related pathologies including cancer. PMID:24575379

  2. Neurotoxicity of Immunosuppressive Therapies in Organ Transplantation

    PubMed Central

    ANGHEL, Daniela; TANASESCU, Radu; CAMPEANU, Ana; LUPESCU, Ioana; PODDA, Giulio; BAJENARU, Ovidiu

    2013-01-01

    ABSTRACT Immunosuppressive agents have revolutionized clinical transplantation medicine, allowing the avoidance of immune system attack on the transplanted graft. Nevertheless, the use of medications such as cyclosporine, tacrolimus and others also brought the side effects of these drugs. Early identification of drug-induced neurotoxicity in transplanted patients and of its specific causes is important, not only because of patient's poor clinical status but because of concomitant systemic and metabolic disorders which may obscure symptoms. Treatment and prognosis are highly dependent on the type of complication and it's early recognition. This review focuses on the clinical entities of neurotoxicity caused by immunosuppressive drugs in transplanted patients. PMID:24371481

  3. Management of patients with hepatitis B who require immunosuppressive therapy

    PubMed Central

    Hwang, Jessica P.; Lok, Anna S.-F.

    2014-01-01

    Patients with chronic HBV infection are at risk of reactivation of HBV should they require immunosuppressive therapies for a variety of clinical settings, including chemotherapy for patients with cancer, immunosuppression for solid organ and stem cell transplant recipients, and use of anti-CD20 antibodies, TNF inhibitors, or corticosteroids in patients with oncological, gastrointestinal, rheumatological or dermatological conditions. The key to preventing HBV reactivation is the identification of patients with HBV infection prior to immunosuppressive therapy, initiation of prophylactic antiviral therapy in patients at moderate or high risk of HBV reactivation, and close monitoring of other patients so that antiviral therapy can be initiated at the first sign of HBV reactivation. Unfortunately, many patients infected with HBV are unaware of their infection or risk factors, and physicians often do not have sufficient time to systematically assess patients for risk factors for HBV prior to starting immunosuppressive therapy. In this article, we review the incidence, risk factors and outcomes of HBV reactivation, and the efficacy of antiviral therapy in preventing its occurrence. We also propose an algorithm for managing patients with HBV infection who require immunosuppressive therapy. PMID:24247262

  4. New Immunosuppressive Therapies in Uveitis Treatment

    PubMed Central

    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

  5. Immunosuppressive Therapy-Related Kaposi Sarcoma

    MedlinePlus

    ... therapy are used to treat Kaposi sarcoma lesions . Photon radiation therapy treats lesions with high-energy light. ... complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information ...

  6. Aggressive Adolescents Benefit from Massage Therapy.

    ERIC Educational Resources Information Center

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Shaw, Jon A.; Rothe, Eugenio M.; Castellanos, Daniel; Mesner, Linda

    2002-01-01

    Seventeen aggressive adolescents were assigned to a massage therapy group or a relaxation therapy group to receive 20-minute therapy sessions, twice a week for five weeks. The massaged adolescents had lower anxiety after the first and last sessions. By the end of the study, they also reported feeling less hostile and they were perceived by their…

  7. Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

    PubMed Central

    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

  8. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  9. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  10. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  11. Phagocytic cell function in response to immunosuppressive therapy.

    PubMed

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  12. Visual loss resulting from immunosuppressive therapy in patients with syphilitic uveitis.

    PubMed

    Afonso, Vivian Cristina Costa; Nascimento, Heloisa; Belfort, Rubens M; Sato, Emilia Inoue; Muccioli, Cristina; Belfort Jr, Rubens

    2015-01-01

    Permanent visual loss can be caused by improper use of immunosuppressive therapy in cases of uveitis without differential diagnosis of syphilitic uveitis. We present four cases of syphilitic uveitis that were incorrectly diagnosed as being secondary to rheumatic diseases and were subsequently treated with immunosuppressive therapy, leading to permanent visual loss. These cases highlight the importance of ruling out syphilis in the differential diagnosis of inflammatory ocular diseases before starting use of immunosuppressive therapy. PMID:26222110

  13. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... therapy. 410.30 Section 410.30 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  14. Periodontitis treatment improves systemic lupus erythematosus response to immunosuppressive therapy.

    PubMed

    Fabbri, Cristiana; Fuller, Ricardo; Bonfá, Eloisa; Guedes, Lissiane K N; D'Alleva, Paulo Sergio R; Borba, Eduardo F

    2014-04-01

    Periodontal disease (POD) may affect rheumatic diseases severity, but there are no data regarding the effect of its treatment on disease activity in SLE patients under immunosuppressive therapy. Forty-nine consecutive SLE patients (SLEDAI ≥ 2) with POD and under corticosteroid and cyclophosphamide pulse therapy (IVCYC) were selected. Periodontal assessment included bleeding gingival index (BGI), probing depth (PD), and probing attachment level (PAL). At entry, POD was defined as BGI > 1 and patients were assigned to groups according to the availability of odontological intervention in TREATED (n = 32) and NOT TREATED (n = 17). SLEDAI and POD parameters were determined at entry and after 3 months. Age, female gender, and race were alike among TREATED and NOT TREATED (p > 0.05). Both groups had also comparable disease duration (10.7 ± 6.8 vs. 11.0 ± 6.6, p = 0.83), IVCYC number (5.8 ± 4.8 vs. 4.5 ± 4.8, p = 0.17), and SLEDAI (5.9 ± 4.2 vs. 6.3 ± 4.3, p = 0.73) as well as POD parameters [BGI (40.8 ± 31.0 vs. 40.7 ± 36.2 %, p = 0.89), PD (1.7 ± 1.8 vs. 1.5 ± 0.60 mm, p = 0.80), and PAL (2.5 ± 1.9 vs. 1.9 ± 1.1 mm, p = 0.18)]. At the end of the study, TREATED group had a significant improvement in SLEDAI (5.9 ± 4.2 vs. 3.4 ± 3.3, p = 0.04) with a paralleled reduction in BGI (40.8 ± 31.0 vs. 15.2 ± 17.2 %, p < 0.01), PD (1.7 ± 1.8 vs. 1.1 ± 0.3 mm, p < 0.01), and PAL (2.5 ± 1.9 vs. 1.7 ± 0.9 mm, p < 0.01). In contrast, SLEDAI (6.3 ± 4.3 vs. 6.0 ± 5.5, p = 0.40) and POD parameters [BGI (p = 0.33), PD (p = 0.91), and PAL (p = 0.39)] remained largely unchanged in NOT TREATED group. Periodontal disease treatment seems to have a beneficial effect in controlling disease activity in SLE patients under immunosuppressive therapy. Therefore, management of this modifiable risk factor is

  15. Immunosuppressive therapy in allograft transplantation: from novel insights and strategies to tolerance and challenges

    PubMed Central

    Ebrahimi, Ammar; Hosseini, Seyed Ahmad

    2014-01-01

    Immunosuppression therapy is the key to successful post-transplantation outcomes. The need for ideal immunosuppression became durable maintenance of long-term graft survival. In spite of current immunosuppressive therapy regimens advances, surgical procedures, and preservation methods, organ transplantation is associated with a long-term poor survival and significant mortality. This has led to an increased interest to optimize outcomes while minimizing associated toxicity by using alternative methods for maintenance immunosuppression, organ rejection treatment, and monitoring of immunosuppression. T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles, have been studied during the last decades. Treg cells are able to inhibit the development of allergen-specific cell responses and consequently play a key role in a healthy immune response to allergens. Mature dendritic cells (DCs) play a crucial role in the differentiation of Tregs, which are known to regulate allergic inflammatory responses. Advance in long-standing allograft outcomes may depend on new drugs with novel mechanisms of action with minimal toxicity. Newer treatment techniques have been developed, including using novel stem cell-based therapies such as mesenchymal stem cells, phagosomes and exosomes. Immunoisolation techniques and salvage therapies, including photopheresis and total lymphoid irradiation have emerged as alternative therapeutic choices. The present review evaluates the recent clinical advances in immunosuppressive therapies for organ transplantation. PMID:26155155

  16. Immunosuppressive Therapy in Immune-Mediated Liver Disease in the Non-Transplanted Patient

    PubMed Central

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  17. Immunosuppressive therapy in immune-mediated liver disease in the non-transplanted patient.

    PubMed

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  18. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  19. Effect of Immunosuppressive Therapy on Proteinogram in Rats

    PubMed Central

    Kędzierska, Karolina; Sindrewicz, Krzysztof; Sporniak-Tutak, Katarzyna; Bober, Joanna; Stańczyk-Dunaj, Małgorzata; Dołęgowska, Barbara; Kaliszczak, Robert; Sieńko, Jerzy; Kabat-Koperska, Joanna; Gołembiewska, Edyta; Ciechanowski, Kazimierz

    2016-01-01

    Background It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. Material/methods The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. Results Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. Conclusions (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively. PMID:27288069

  20. Effect of Immunosuppressive Therapy on Proteinogram in Rats.

    PubMed

    Kędzierska, Karolina; Sindrewicz, Krzysztof; Sporniak-Tutak, Katarzyna; Bober, Joanna; Stańczyk-Dunaj, Małgorzata; Dołęgowska, Barbara; Kaliszczak, Robert; Sieńko, Jerzy; Kabat-Koperska, Joanna; Gołembiewska, Edyta; Ciechanowski, Kazimierz

    2016-01-01

    BACKGROUND It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. RESULTS Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. CONCLUSIONS (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively. PMID:27288069

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

    PubMed Central

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    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. PMID:24926266

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26315930

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

    PubMed

    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. PMID:25572607

  4. Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

    PubMed Central

    Lee, Ju-Yeun; Kim, Yul Hee; Kim, Hyang Sook; Lee, Hye Suk; Lee, Byung Koo; Kim, Hyeyoung; Choi, Young Rok; Hong, Geun; Lee, Kwang-Woong; Suh, Kyung-Suk

    2014-01-01

    Background/Aims The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. Methods Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD). Results The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). Conclusions Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients. PMID:25032186

  5. Pharmacodynamic monitoring of immunosuppressive effects indicates reduced cyclosporine activity during telaprevir therapy.

    PubMed

    Roos, Katja; Gotthardt, Daniel; Giese, Thomas; Schnitzler, Paul; Stremmel, Wolfgang; Czock, David; Eisenbach, Christoph

    2014-09-01

    Drug interactions with immunosuppressive drugs are a major problem associated with protease inhibitor-based antiviral triple therapy for hepatitis C virus (HCV) reinfection after liver transplantation. In this retrospective cohort study, we analyzed biomarkers of the immunosuppressive effects of cyclosporine A (CSA) by quantifying nuclear factor of activated T cells (NFAT)-regulated gene expression during telaprevir (TVR) therapy in 5 liver transplant patients. Furthermore, dose adjustments and blood concentrations of CSA as well as the clinical course were analyzed. We observed a clear impact of TVR not only on doses and blood concentrations but also on the immunosuppressive effects of CSA. Despite apparently adequate CSA trough concentrations, the CSA peak concentration decreased to 68% (range = 44%-90%). This was associated with a 1.9-fold (1.6- to 4.1-fold) increase in the residual gene activity of NFAT-regulated genes, which indicated reduced immunosuppressive activity of CSA with TVR co-medication. The median dose of CSA was reduced to 25% (range = 16%-48%) and 31% (range = 22%-64%) after 1 and 2 weeks, respectively. The CSA drug clearance was reduced to 38.7% (range = 31.0%-49.4%). We report excellent antiviral efficacy. At the end of the observation period, all patients were HCV RNA-negative (1 patient at 18 weeks, 1 patient at 12 weeks, and 3 patients at 4 weeks after the end of therapy). Safety was acceptable, with mild acute rejection and reactivation of cytomegalovirus being the most serious adverse events. One patient with histologically proven recurrent cholestatic hepatitis before therapy underwent retransplantation during the course of antiviral therapy. In conclusion, the immunomonitoring of NFAT-regulated gene expression indicated reduced immunosuppressive activity of CSA during antiviral therapy with TVR in our cohort of liver transplant patients. Thus, the immunosuppressive effects of CSA may be overestimated if one is looking

  6. Interleukin-2 therapy reverses some immunosuppressive effects of skeletal unloading

    NASA Technical Reports Server (NTRS)

    Armstrong, Jason W.; Balch, Signe; Chapes, Stephen K.

    1994-01-01

    Using antiorthostatic suspension, we characterized hematopoietic changes that may be responsible for the detrimental effect of skeletal unloading on macrophage development. Skeletally unloaded mice had suppressed macrophage development in unloaded and loaded bones, which indicated a systemic effect. Bone marrow cells from unloaded mice secreted less macrophage colony-stimulating factor and interleukin-6 than control mice. Additionally, T-lymphocyte proliferation was reduced after skeletal unloading. We show that polyethylene glycol-interleukin-2 therapy reversed the effects of skeletal unloading on macrophage development and cell proliferation.

  7. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood.

    PubMed

    Yoshimi, Ayami; van den Heuvel-Eibrink, Marry M; Baumann, Irith; Schwarz, Stephan; Simonitsch-Klupp, Ingrid; de Paepe, Pascale; Campr, Vit; Kerndrup, Gitte Birk; O'Sullivan, Maureen; Devito, Rita; Leguit, Roos; Hernandez, Miguel; Dworzak, Michael; de Moerloose, Barbara; Stary, Jan; Hasle, Henrik; Smith, Owen P; Zecca, Marco; Catala, Albert; Schmugge, Markus; Locatelli, Franco; Führer, Monika; Fischer, Alexandra; Guderle, Anne; Nöllke, Peter; Strahm, Brigitte; Niemeyer, Charlotte M

    2014-04-01

    Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090). PMID:24162791

  8. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

    PubMed Central

    Yoshimi, Ayami; van den Heuvel-Eibrink, Marry M.; Baumann, Irith; Schwarz, Stephan; Simonitsch-Klupp, Ingrid; de Paepe, Pascale; Campr, Vit; Kerndrup, Gitte Birk; O’Sullivan, Maureen; Devito, Rita; Leguit, Roos; Hernandez, Miguel; Dworzak, Michael; de Moerloose, Barbara; Starý, Jan; Hasle, Henrik; Smith, Owen P.; Zecca, Marco; Catala, Albert; Schmugge, Markus; Locatelli, Franco; Führer, Monika; Fischer, Alexandra; Guderle, Anne; Nöllke, Peter; Strahm, Brigitte; Niemeyer, Charlotte M.

    2014-01-01

    Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090) PMID:24162791

  9. The critically ill immunosuppressed patient

    SciTech Connect

    Parrillo, J.E.; Masur, H. )

    1987-01-01

    This book discusses the papers on the diagnosis and management of immunosuppressed patient. Some of the topics are: life-threatening organ failure in immunosuppressed patients; diagnosis and therapy of respiratory disease in the immunosuppressed patient; CNS complication of immunosuppression; infections; antineoplastic therapy of immunosuppressed patient; radiation therapy-issues in critically ill patient; AIDS; and management of bone marrow transplant patients.

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

    PubMed

    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. PMID:26872631

  11. Selection and use of immunosuppressive therapies after liver transplantation: current German practice.

    PubMed

    Herzer, Kerstin; Strassburg, Christian P; Braun, Felix; Engelmann, Cornelius; Guba, Markus; Lehner, Frank; Nadalin, Silvio; Pascher, Andreas; Scherer, Marcus N; Schnitzbauer, Andreas A; Zimmermann, Tim; Nashan, Björn; Sterneck, Martina

    2016-05-01

    In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus-based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3-6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult-to-treat patient subpopulations. PMID:26855333

  12. Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy

    PubMed Central

    De Vlaminck, Iwijn; Khush, Kiran K.; Strehl, Calvin; Kohli, Bitika; Neff, Norma F.; Okamoto, Jennifer; Snyder, Thomas M.; Weill, David; Bernstein, Daniel; Valantine, Hannah A.; Quake, Stephen R.

    2014-01-01

    Summary There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with a post-transplant therapy that combines immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients), and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment, and offer a potential application of the virome state to predict immunocompetence. PMID:24267896

  13. Successful treatment of renal allograft and bladder malakoplakia with minimization of immunosuppression and prolonged antibiotic therapy.

    PubMed

    Graves, Angela L; Texler, Michael; Manning, Laurens; Kulkarni, Hemant

    2014-04-01

    Malakoplakia is an unusual granulomatous inflammatory disorder associated with diminished bactericidal action of leucocytes that occurs in immunosuppressed hosts. Cases of renal allograft malakoplakia are generally associated with a poor graft and patient survival. We present the case of a 56-year-old female with allograft and bladder malakoplakia occurring two years after renal transplantation complicated by an early antibody mediated rejection. Following a number of symptomatic urinary tract infections caused by resistant Gram-negative bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall. Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased, prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully monitored to maintain trough serum concentrations of 2-4 μg/L. Concurrently, she received a prolonged course of intravenous antibiotics followed by 13 months of dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach resulted in almost complete resolution of allograft malakoplakia lesions and sustained regression of bladder lesions on cystoscopy with histological resolution in bladder lesions. Her renal function has remained stable throughout the illness. If treated with sustained antimicrobial therapy and reduction of immunosuppression, cases of allograft malakoplakia may not necessarily be associated with poor graft survival. PMID:24460630

  14. Phlyctenular keratoconjunctivitis – an atypically severe case treated with systemic biologic immunosuppressive therapy

    PubMed Central

    Valério Sequeira Valadares, Joana; Bastos-Carvalho, Ana; Pedroso Franco, José Manuel; Mourão, Ana Filipa; Monteiro-Grillo, Manuel

    2014-01-01

    Purpose: To report an atypically severe and refractory phlyctenular keratoconjunctivitis case treated successfully with systemic biologic immunosuppressive therapy. Methods: A 10-year-old female was followed in the ophthalmology clinic for three years for a severe form of bilateral PKC. The patient was treated for blepharitis and intestinal parasitosis, and underwent topical corticosteroid therapy, followed by subconjunctival injections and systemic corticosteroids with no clinical improvement. An association of topical cyclosporine A and oral methotrexate had no clinical response either. Phlyctenae of the cornea remained evident with neovascularization, progressive peripheral corneal thinning and occasional anterior chamber reaction. Results: The patient was treated with a combination of infliximab and methotrexate and corticosteroid therapy was tapered, with a fast and sustained resolution of the symptoms and corneal signs. Eleven months past initiation of the treatment, the patient remains asymptomatic and without any recurrence of the disease. Conclusion: Phlyctenular keratoconjunctivitis may present with a broad spectrum of symptoms and signs, and its severity varies significantly. In cases of severe PKC, which are refractory to conventional therapy, systemic biologic immunosuppressive therapy may be a valuable alternative.

  15. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

    PubMed Central

    Gassas, Adam; Min, Weixian; Evans, A. Wayne; Carter, Susan; Sándor, George K.; Grunebaum, Eyal

    2011-01-01

    Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model. PMID:22046567

  16. Resistance to Antiangiogenic Therapy Is Associated with an Immunosuppressive Tumor Microenvironment in Metastatic Renal Cell Carcinoma.

    PubMed

    Liu, Xian-De; Hoang, Anh; Zhou, Lijun; Kalra, Sarathi; Yetil, Alper; Sun, Mianen; Ding, Zhiyong; Zhang, Xuesong; Bai, Shanshan; German, Peter; Tamboli, Pheroze; Rao, Priya; Karam, Jose A; Wood, Christopher; Matin, Surena; Zurita, Amado; Bex, Axel; Griffioen, Arjan W; Gao, Jianjun; Sharma, Padmanee; Tannir, Nizar; Sircar, Kanishka; Jonasch, Eric

    2015-09-01

    Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer, and antiangiogenic therapy is the current mainstay of treatment. Patients with RCC develop innate or adaptive resistance to antiangiogenic therapy. There is a need to identify biomarkers that predict therapeutic resistance and guide combination therapy. We assessed the interaction between antiangiogenic therapy and the tumor immune microenvironment and determined their impact on clinical outcome. We found that antiangiogenic therapy-treated RCC primary tumors showed increased infiltration of CD4(+) and CD8(+) T lymphocytes, which was inversely related to patient overall survival and progression-free survival. Furthermore, specimens from patients treated with antiangiogenic therapy showed higher infiltration of CD4(+)FOXP3(+) regulatory T cells and enhanced expression of checkpoint ligand programed death-ligand 1 (PD-L1). Both immunosuppressive features were correlated with T-lymphocyte infiltration and were negatively related to patient survival. Treatment of RCC cell lines and RCC xenografts in immunodeficient mice with sunitinib also increased tumor PD-L1 expression. Results from this study indicate that antiangiogenic treatment may both positively and negatively regulate the tumor immune microenvironment. These findings generate hypotheses on resistance mechanisms to antiangiogenic therapy and will guide the development of combination therapy with PD-1/PD-L1-blocking agents. PMID:26014097

  17. Clinical Study of Porokeratosis Associated with Immunosuppressive Therapy in Renal Transplant Recipients

    PubMed Central

    Han, Ye Won; Kim, Yeon Jeong; Kim, Hyung Ok

    2008-01-01

    Background The etiology of porokeratosis (PK) remains unknown, but immunosuppression is known to be a factor in the pathogenesis of PK and it may also exacerbate PK. Objective The aim of this study was to examine the clinical characteristics of PK associated with immunosuppressive therapy in renal transplant recipients. Methods A total of 9 renal transplant patients diagnosed with biopsy-proven PK from January 2001 to December 2006 were enrolled. The authors analyzed the patient and medication histories, clinical characteristics, and associated diseases. Results The ages of the 9 patients ranged from 38 to 67 years (mean 52 years). All received multi-drug regimens comprised of two or three immunosuppressive agents (steroids, cyclosporine, mycophenolate mofetil, azathioprine and/or tacrolimus). Times between transplantation and the onset of PK ranged from 2 to 9 years (mean 4.1 years). No family history of PK or a history of intense sun-exposure was elicited. The number of the lesions was less than ten in 8 of the 9. Lesions were mainly located in the extremities, though some affected the trunk or neck (3). Three patients had disseminated superficial actinic PK (DSAP), PK Mibelli, or both types. Associated diseases included verruca (4), recurrent herpes simplex (1), actinic keratosis (1), and cutaneous B cell lymphoma (1). Conclusion The three clinical patterns of PK occurred equally in our patients, namely, coexistent PK Mibelli and DSAP, or the DSAP and Mibelli types as independent forms. Our findings support the notion that the different variants of PK be viewed as parts of a heterogeneous clinical spectrum. Further studies are needed in order to establish the clinical patterns of PK in immunosuppressed patients. PMID:27303185

  18. [Immunosuppressive therapy or chemotherapy-induced reactivation of hepatitis B virus infection].

    PubMed

    Sato, Kazuya

    2011-02-01

    Immunosuppressive treatments, such as rituximab-containing chemotherapy or stem cell transplantation, have been widely performed following recent developments in cancer therapy. Immunosuppressive therapy or chemotherapy(IS/CT)-induced reactivation of the hepatitis B virus(HBV)in HBsAg-positive HBV-carriers is a well-known phenomenon. It has recently been demonstrated that HBV-reactivation also occurs in HBV-resolved patients who are negative for HBsAg, and positive for HBsAb and/or HBcAb. This is because de novo hepatitis B, which occurs in HBV-resolved patients with a recurrence of HBV hepatitis, have a high risk of fulminant hepatitis with an extremely poor prognosis. In this regard, prevention a guideline for IS/ CT-induced HBV-reactivation was established in Japan. However, the incidence of, and risk factors for, IS/CT-induced HBV- reactivation in HBV-resolved patients in Japan has not yet been elucidated. We retrospectively analyzed IS/CT-induced HBV- reactivation in resolved HBV-patients with hematological disorders in our hospital. Reactivation occurred in 5. 0%patients(5/ 101), and administration of more than 2 regimens for the hematological disorder was identified as an independent risk factor for HBV-reactivation in multivariate analysis. Further investigation of the risk factors for HBV-reactivation and the efficacy of the guideline should be performed during multicenter prospective study. PMID:21368477

  19. Invasive aspergillosis successfully treated by combined antifungal therapy and immunosuppressive monotherapy two months following heart transplantation

    PubMed Central

    Żabicki, Bartłomiej; Baszyńska-Wachowiak, Hanna; Straburzyńska-Migaj, Ewa; Juszkat, Robert; Grajek, Stefan; Jemielity, Marek

    2016-01-01

    Invasive aspergillosis is becoming increasingly prevalent, especially following transplantation. Invasive aspergillosis is associated with mortality. Successful therapy is related to early diagnosis and proper therapy. We present the case of a 61-year-old man suffering from invasive aspergillosis 2 months following heart transplantation. He was suffering from hypertrophic cardiomyopathy and he underwent orthotropic heart transplantation. He was readmitted to the Department of Cardiology 69 days following transplantation due to symptoms of productive cough for 5 days. It was accompanied by chest pain, shortness of breath, and fever up to 39°C. He was slightly cyanotic and confused on physical examination. The patient's status deteriorated within the following 2 days. On bronchoscopic specimen examinations Aspergillus mould filaments were detected and the serum galactomannan index was 12.162. His blood saturation decreased to 85%. C-reactive protein serum level increased to 273 mg/l. The patient was admitted to the intensive care unit and intubated due to severe respiratory insufficiency. Computed tomography revealed massive, mostly homogeneous consolidation. The patient was treated with 200 mg of voriconazole and 50 mg of caspofungin daily. Caspofungin therapy was continued for 23 days and voriconazole was administered parenterally for 62 days. Voriconazole therapy was continued orally for 9 months. During combined antifungal therapy, the galactomannan serum index constantly decreased from 12.1 to 0.33 (end-point of caspofungin therapy) and to 0.23 (end-point of voriconazole parenteral administration). His immunosuppressive therapy was limited to calcineurin inhibitor (tacrolimus) monotherapy. Post-treatment imaging 9 months after diagnosis confirmed the efficacy of therapy as a lack of pulmonary infiltration associated with left apical peribronchial scarring as a result of treatment. The present case proved the efficiency of combined (voriconazole and caspofungin

  20. Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review-Screened

    PubMed Central

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Context Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions. Evidence Acquisition Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr. Results It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of

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

    PubMed Central

    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

    2014-01-01

    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 (P<0.001). Multivariate analysis showed that telomere length shorter than −1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19–115; P<0.001), platelet count at diagnosis less than 25×109/L (HR: 13.9; 95%CI: 2.00–96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15–20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia. PMID:24816243

  2. Role of Exclusive Enteral Nutrition in the Preoperative Optimization of Patients With Crohn's Disease Following Immunosuppressive Therapy

    PubMed Central

    Li, Yi; Zuo, Lugen; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Gu, Lili; Guo, Zhen; Cao, Lei; Li, Ning; Li, Jieshou

    2015-01-01

    Abstract We conducted a study to evaluate the impact of the exclusive enteral nutrition (EEN) on perioperative outcome in Crohn's disease (CD) patients following immunosuppressive therapy. Patients with CD followed at a referral center between January 2001 and March 2014 who underwent abdominal surgery were identified. Patients were divided into 4 groups: patients not exposed to immunosuppressive agents in the previous 8 weeks before surgery (group 1); patients received immunosuppressive medications without preoperative drug-free interval (group 2); patients had preoperative immunosuppressants-free interval (group 3); patients treated with adding EEN to preoperative immunosuppressants-free interval regimen (group 4). Urgent operation requirement, stoma creation, postoperative complications, readmission, and reoperation were compared in patients among groups. Overall, 708 abdominal surgeries performed in 498 CD patients were identified. Three hundred seventy-six (53.11%) surgeries performed in those receiving preoperative immunosuppressive medications. Compared with other groups, group 2 had increased postoperative complications, more frequent urgent operation, and higher rate of stoma creation. Patients in group 4 were found to have better outcome including lower rate of stoma creation (P < 0.05), and decreased incidence of postoperative complications (P < 0.05) compared with group 2 and group 3. Additionally, decreased urgent operation requirement (P < 0.05) and extended preoperative drug-free interval (P < 0.001) were observed in the group 4 than those in the group 3. Preoperative optimization of CD following immunosuppressive therapy by EEN prolongs the immunosuppressants-free interval, reduces the risk of urgent surgery and reoperation, and most importantly, decreases complications after abdominal surgery. PMID:25654387

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

    PubMed Central

    Xue, Yu; Jiang, Li; Wan, Wei-Guo; Chen, Yu-Ming; Zhang, Jiong; Zhang, Zhen-Chun

    2016-01-01

    Background: Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China. Methods: Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis. 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 < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P

  4. Immunosuppressive therapy for patients with Down syndrome and idiopathic aplastic anemia.

    PubMed

    Suzuki, Kyogo; Muramatsu, Hideki; Okuno, Yusuke; Narita, Atsushi; Hama, Asahito; Takahashi, Yoshiyuki; Yoshida, Makoto; Horikoshi, Yasuo; Watanabe, Ken-Ichiro; Kudo, Kazuko; Kojima, Seiji

    2016-07-01

    Idiopathic aplastic anemia (AA) is a rare hematological complication of Down syndrome (DS). The safety and efficacy of immunosuppressive therapy (IST) in individuals with DS remain unknown. We used a standard regimen of IST, comprising antithymocyte globulin and cyclosporine A, to treat three children with DS and idiopathic acquired AA. Two patients achieved a hematological (complete or partial) response and became transfusion independent at the final follow-up. The third patient failed to respond to IST and underwent bone marrow transplantation from a human leukocyte antigen (HLA)-mismatched unrelated donor. None of the patients experienced severe or unexpected adverse events during IST. Our experience suggests that IST is a safe and reasonable treatment, even in individuals with DS who suffer from AA and lack an HLA-matched sibling donor. PMID:27107757

  5. Outcomes of nonsurgical periodontal therapy in severe generalized aggressive periodontitis

    PubMed Central

    2014-01-01

    Purpose Aggressive periodontitis, especially in its severe form, was traditionally considered to have an unfavourable prognosis. It required a complex treatment and its stabilization was often achieved by surgical therapy. The aim of this study was to investigate the results of nonsurgical periodontal treatment in severe generalized forms of aggressive periodontitis. Methods Patients with advanced generalized aggressive periodontitis were included in the study. Probing depth (PD) of pockets ≥7 mm and clinical attachment level (CAL) of sites with attachment loss ≥5 mm were measured at baseline before nonsurgical periodontal treatment, at re-evaluation, and after treatment. The following other parameters were recorded: resolution of inflammation and bone fill. We compared the baseline values with re-evaluation and posttreatment values using the Friedman test. The Wilcoxon test with the Bonferroni correction was used for both re-evaluation and posttreatment values. Results Seven patients with 266 periodontal sites were examined. A significant difference was found between values, reported as medians with interquartile ranges, for PD at baseline (7.94 [7.33-8.19] mm) and both re-evaluation (4.33 [3.63-5.08] mm) and posttreatment (3.54 [3.33-4.11] mm) values (P=0.002). A significant difference was also found between values for CAL at baseline (9.02 [7.5-9.2] mm) and both re-evaluation (6.55 [6.30-6.87] mm) and posttreatment (6.45 [5.70-6.61] mm) (P=0.002). Inflammation was resolved and angular bone defects were repaired in all cases. Conclusions These therapeutic results suggest that this form of periodontitis could have positive outcomes after nonsurgical periodontal treatment. The reparative potential of tissue affected by severe aggressive periodontitis should encourage clinicians to save apparently hopeless teeth in cases of this form of periodontitis. Graphical Abstract PMID:25177522

  6. Autoimmune Hepatitis: Progress from Global Immunosuppression to Personalised Regulatory T Cell Therapy

    PubMed Central

    Than, Nwe Ni; Jeffery, Hannah C.; Oo, Ye H.

    2016-01-01

    Autoimmune hepatitis (AIH) is an immune mediated liver injury. The precise aetiology of AIH is still unknown but current evidence suggests both genetic and environmental factors are involved. Breakdown in peripheral self-tolerance, and impaired functions of FOXP3+ regulatory T cell along with effector cell resistance to suppression at the tissue level seem to play an important role in AIH immunopathogenesis. AIH is predominantly a T lymphocytes driven disease but B lymphocytes are also involved in the immunopathology. Innate immune cells are crucial in the initial onset of disease and their response is followed by adaptive T (Th1, Th17, and cytotoxic T cells) and B cell responses evidenced by liver histology and peripheral blood serology. Standard treatment regimens involving steroid and immunosuppressive medications lead to global immune suppression requiring life-long therapy with many side effects. Biologic therapies have been attempted but duration of remission is short-lived. Future direction of diagnosis and treatment for AIH should be guided by “omics” and the immunology profile of the individual patient and clinicians should aim to deliver personalised medicine for their patients. Cell therapy such as infusion of autologous, antigen-specific, and liver-homing regulatory T cells to restore hepatic immune tolerance may soon be a potential future treatment for AIH patients. PMID:27446862

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

    PubMed Central

    Foroutan, Naghmeh; Rasekh, Hamid R; Salamzadeh, Jamshid; Jamshidi, Hamid R; Nafar, Mohsen

    2013-01-01

    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 lower required doses of MMF related to SRL based therapies were major reasons for this saving budgetary impact. PMID:24159260

  8. Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia.

    PubMed

    Narita, Atsushi; Kojima, Seiji

    2016-08-01

    The decision to select hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) as initial therapy in acquired aplastic anemia (AA) is currently based on patient age and the availability of a human leukocyte antigen (HLA)-matched donor. Although IST is a promising treatment option, the ability to predict its long-term outcomes remains poor due to refractoriness, relapses, and the risk of clonal evolution. Several predictive biomarkers for response to IST have been posited, including age, gender, pre-treatment blood cell counts, cytokines, gene mutations, paroxysmal nocturnal hemoglobinuria (PNH), and telomere length (TL). While previous studies have provided substantial biological insights into the utility of IST, the prognostic power of the reported biomarkers is currently insufficient to contribute to clinical decision making. Recently, a large retrospective analysis proposed the combination of minor PNH clones and TL as an efficient predictor of IST response. Identification of a reliable predictor would provide a useful tool for determining the most appropriate treatment choice for AA patients, including up-front HSCT from HLA-matched unrelated donor. The present review summarizes studies evaluating the utility of biomarkers in predicting the clinical response to IST of patients with AA, and provides a baseline for prospective studies aimed at validating previously reported biomarkers. PMID:27091471

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

    PubMed

    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. PMID:27278666

  10. [Pro and contra: aggressive or conservative thrombosis therapy? - Pro aggressive thrombosis therapy].

    PubMed

    Grommes, J

    2014-10-01

    The post-thrombotic syndrome (PTS), long-term sequelae of a deep vein thrombosis (DVT), reduces quality of life and is of great socio-economic importance. Despite conservative treatment which does not directly facilitate recanalization more than 25% of patients develop PTS. Early thrombus removal may decrease the incidence and severity of PTS. Although the evidence for surgical thrombectomy is weak which allows an early and rapid recanalization, this therapy appears to reduce the risk of PTS and iliofemoral thrombosis. Systemic thrombolysis can reduce the incidence of PTS but it is no longer recommended due to serious bleeding complications. Previous studies with new endovascular catheter-guided procedures allowing local application of thrombolysis and thrombus aspiration displayed promising results. However, so far one prospective randomised study (CaVent study) with long-term results has revealed a significant reduction of PTS. The current evidence recommends early thrombus removal for patients at high risk for PTS. New endovascular procedures such as catheter-guided thrombolysis allow rapid thrombus removal but more prospective randomised studies are necessary to ensure the long-term success of this therapy. PMID:25313889

  11. Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis

    PubMed Central

    Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

    2011-01-01

    OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975

  12. Immunosuppressive Medications

    PubMed Central

    2016-01-01

    Immunosuppressive agents are commonly used in the nephrologist’s practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist. PMID:26170177

  13. Immunosuppressive Medications.

    PubMed

    Wiseman, Alexander C

    2016-02-01

    Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist. PMID:26170177

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

    PubMed Central

    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

  15. Immunization of Children Receiving Immunosuppressive Therapy for Cancer or Hematopoietic Stem Cell Transplantation

    PubMed Central

    Shetty, Avinash K.; Winter, Mary A.

    2012-01-01

    In the past 3 decades, the number of immunocompromised children has increased steadily because of dramatic improvement in survival rates in certain malignancies as a result of intensive curative treatment regimens and an increase in the number of children undergoing life-saving hematopoietic stem cell transplantation (HSCT). Children receiving immunosuppressive therapy for cancer, as well as HSCT recipients, will benefit from vaccination but warrant close evaluation for a variety of reasons, such as the risk of developing severe infections, serious adverse events following certain vaccines, and decreased vaccine efficacy caused by poor immune response to vaccination. Various professional organizations have published vaccination guidelines for immunocompromised patients. Given their heterogeneity, recommendations for the immunization of immunocompromised patients may not be universally applicable. The safety of many commonly used vaccines has not been established in immunocompromised children. In addition, no large-scale vaccine studies have evaluated the clinical outcome of disease prevention in this population. All killed vaccines are generally safe, while live vaccines may be administered to immunocompromised children in select circumstances, depending on the degree of altered immunocompetence and the underlying primary condition. Healthcare providers should be knowledgeable about the indications, contraindications, and precautions for vaccine administration in immunocompromised patients. To protect immunocompromised patients, all family, household contacts, and healthcare workers should also be immunized with all routinely recommended vaccines. Pediatricians play a crucial role in identifying and effectively communicating the risks and benefits of vaccines to immunocompromised patients and their parents. PMID:23049460

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25107891

  17. Coexistence of normal and clonal haemopoiesis in aplastic anaemia patients treated with immunosuppressive therapy.

    PubMed

    Piaggio, G; Podestà, M; Pitto, A; Sessarego, M; Figari, O; Fugazza, G; Benvenuto, F; Bruno, B; Van Lint, M T; Truini, M; Frassoni, F; Bacigalupo, A

    1999-12-01

    Cytogenetic abnormalities and paroxysmal nocturnal haemoglobinuria (PNH) phenotype are frequent findings in aplastic anaemia patients treated with immunosuppressive therapy (IST). In this study we investigated whether the appearance of clonal haemopoiesis influences patient outcome and survival. 97 patients entered this study and were followed from the onset of the disease for a median follow-up (FU) of 53 months. 93% are alive, 56% achieved complete remission, 30% partial remission, both transfusion independent, and 14% did not respond. Three groups were identified: (A) patients without evidence of emerging clones (71/97); (B) patients who acquired chromosomal abnormalities (13/97); (C) patients who showed low expression of glycosyl phosphatidylinositol anchored proteins (GPI-AP) (PNH phenotype) at presentation or later (16/97). Three patients showed both PIG-AP deficiency and chromosomal abnormalities. The actuarial survival of patients without clonal haemopoiesis (n = 71) at 6 years was 95%, for patients with chromosomal abnormalities (n = 13), 88%, and for patients with PIG-AP deficiency (n = 16), 89%. There was no difference in the probability of becoming transfusion independent in the three groups (93%, 92% and 88% respectively). This study confirmed that a proportion of severe aplastic anaemia (SAA) patients exhibit clonal markers during the time after IST, often coexisting with cytogenetically or phenotypically normal haemopoiesis. There was no significant clinical impact of these abnormalities on transfusion independence and survival at the median follow-up of 4 years. PMID:10583249

  18. [Successful bosentan therapy in a case of pulmonary arterial hypertention developed during immunosuppressive therapy for lupus nephritis].

    PubMed

    Ueda, Yo; Takahashi, Yuko; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2011-01-01

    We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized. PMID:21628852

  19. Nanoparticles and direct immunosuppression.

    PubMed

    Ngobili, Terrika A; Daniele, Michael A

    2016-05-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

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

    PubMed Central

    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. Aggression control therapy for violent forensic psychiatric patients: method and clinical practice.

    PubMed

    Hornsveld, Ruud H J; Nijman, Henk L I; Hollin, Clive R; Kraaimaat, Floor W

    2008-04-01

    Aggression control therapy is based on Goldstein, Gibbs, and Glick's aggression replacement training and was developed for violent forensic psychiatric in- and outpatients (adolescents and adults) with a (oppositional-defiant) conduct disorder or an antisocial personality disorder. First, the conditions for promoting "treatment integrity" are examined. Then, target groups, framework, and procedure are described in detail, followed by the most important clinical findings during the period 2002 to 2006. Finally, new programme developments are mentioned, with aggression control therapy as a starting point. PMID:17636205

  2. Reinforcement Behavior Therapy by Kindergarten Teachers on Preschool Children’s Aggression: A Randomized Controlled Trial

    PubMed Central

    Yektatalab, Shahrzad; Alipour, Abdolrasool; Edraki, Mitra; Tavakoli, Pouran

    2016-01-01

    Background: Aggression is a kind of behavior that causes damage or harm to others. The prevalence of aggression is 8–20% in 3–6 years old children. The present study aimed to assess the effect of training kindergarten teachers regarding reinforcement behavior therapy on preschoolers’ aggression. Methods: In this cluster randomized control trial, 14 out of 35 kindergarten and preschool centers of Mohr city, Iran, were chosen using random cluster sampling and then randomly assigned to an intervention and a control group. All 370 kindergarten and preschool children in 14 kindergarten were assessed by preschoolers’ aggression questionnaire and 60 children who obtained a minimum aggression score of 117.48 for girls and 125.77 for boys were randomly selected. The teachers in the intervention group participated in 4 educational sessions on behavior therapy and then practiced this technique under the supervision of the researcher for two months. Preschoolers’ aggression questionnaire was computed in both intervention and control groups before and after a two-month period. Results: The results demonstrated a significant statistical difference in the total aggression score (P=0.01), verbal (P=0.02) and physical (P=0.01) aggression subscales scores in the intervention group in comparison to the control group after the intervention. But the scores of relational aggression (P=0.09) and impulsive anger (P=0.08) subscales were not statistically different in the intervention group compared to the controls. Conclusion: This study highlighted the importance of teaching reinforcement behavior therapy by kindergarten teachers in decreasing verbal and physical aggression in preschoolers. Trial Registration Number: IRCT2014042617436N1 PMID:26793733

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

    PubMed Central

    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

  4. [Anti-inflammatory and immunosuppressive effects of laser therapy in patients with rheumatoid arthritis].

    PubMed

    Tupikin, G V

    1985-01-01

    The clinical and laboratory findings were examined of 10 patients with seropositive rheumatoid arthritis (RA) treated with a first applied technique of intravenous irradiation of the circulating blood with helium-neon laser combined with external irradiation of the inflamed joints. A distinct antiinflammatory and immunosuppressant effect was attained in all the RA patients. In 80% of the test subjects, the rheumatoid blood factor reduced to 1:20 titres. The treatment method did not cause any side effects or complications and shortened the time of the patients' stay at hospital. PMID:4071434

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

    PubMed Central

    Galipeau, Jacques; Nooka, Ajay K.

    2013-01-01

    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. PMID:24350294

  6. Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy.

    PubMed

    Al-Taei, Saly; Banner, Russell; Powell, Ned; Evans, Mererid; Palaniappan, Nachi; Tabi, Zsuzsanna; Man, Stephen

    2013-12-01

    Oropharyngeal cancer (OPC) is a type of squamous cell head and neck cancer that is often associated with human papillomavirus (HPV) infection, suggesting the potential for immunotherapeutic targeting of HPV antigens. This study aimed to determine the effect of radical therapy on HPV-specific T cells and other immune parameters in 20 OPC patients, as a prelude to future immunotherapy studies. HPV DNA could be detected in 9/12 available tissue samples (8/9 HPV(+) samples were also p16(+)). HPV-specific T cell responses against HPV16 E6 and E7 peptides were detected by enzyme-linked immunoSPOT in 10/13 and 8/13 evaluable patients, respectively, but did not appear to correlate with HPV status. Post-treatment, both HPV E6 and E7 T cell responses were decreased (4/13 and 2/13 patients, respectively). These reductions in T cell response could not be explained by a concurrent decrease in memory T cells whose absolute numbers were relatively unaffected by radical therapy (27,975 vs. 25,661/10(5) PBMC) despite a significant decrease in overall lymphocyte counts (1.74 vs. 0.69 × 10(9)/L). Instead, there were significant increases in regulatory T cells (3.7 vs. 6.8 %) and a population of myeloid-derived suppressor cells (CD14(-)HLA-DR(-)CD15(hi), 12.38 vs. 21.92 %). This suggests that immunosuppression may contribute to the reduction in HPV-specific T cell responses post-treatment, although study of larger patient cohorts will be required to test whether this affects clinical outcome. Overall these findings suggest that HPV-targeted immunotherapy in post-therapy OPC patients will require multiple strategies to boost T cell immunity and to overcome the influence of immunosuppressive cells. PMID:24146146

  7. First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

    PubMed Central

    Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

    2011-01-01

    Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

  8. Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy

    PubMed Central

    Hohberger, Bettina; Rudolph, Michael; Bergua, Antonio

    2015-01-01

    Purpose Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. Case Report A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. Results Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. Conclusion Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC. PMID:26955337

  9. The Pharmacology of Immunosuppression

    PubMed Central

    2009-01-01

    Objective To provide students with a comprehensive, integrated presentation on the pharmacology of immuosuppression. Design Course content on the pharmacology of immunosuppression relating to organ transplantation and treatment of autoimmune disorders was presented in integrated sequence modules that included content from pharmacology, medicinal chemistry, and therapeutics. Weekly recitation sessions and active-learning exercises were incorporated to allow students to apply the information they learned to integrated patient cases and stimulate involvement and critical thinking. Fundamental material related to the components and functions of the immune system was presented to students early in curriculum with courses such as biochemistry, pathophysiology, and immunology/microbiology. Assessment Comprehensive examinations, in-class quizzes, written case submissions, case discussions, review exercises, and group exercises were used to assess student learning. Conclusion Students at South University received a comprehensive and detailed understanding of all aspects relating to immunosuppressive therapy. This was accomplished by integrating instruction on immunosuppressive therapy from various disciplines. PMID:20221337

  10. Immunosuppressive therapy for recurrent aborters with positive antiphospholipid antibodies and alteration of 6ketoPGF1 alpha/TXB2 ratio.

    PubMed

    Takakuwa, K; Arakawa, M; Honda, K; Imai, T; Tamura, M; Kurabayashi, T; Tanaka, K

    1997-01-01

    Twelve women (13 pregnancies) with antiphospholipid antibodies (APA) who had suffered from two or more recurrent spontaneous abortions or fetal deaths and had successful pregnancy outcomes after immunosuppressive therapy were studied. APA titers were determined by enzyme-linked immunosorbent assay against cardiolipin, phosphatidyl serine and phosphatidyl inositol. Plasma levels of 6ketoprostaglandin F1 alpha (6ketoPGF1 alpha) and thromboxane B2 (TXB2) were determined by radioimmunoassay. All of the 13 pregnancies resulted in term delivery. None of the 13 patients suffered from pregnancy-induced hypertension, and only one showed intrauterine growth retardation. A significant decrease of APA titer was observed after immunosuppressive therapy. The 6ketoPGF1 alpha/TXB2 ratios before the therapy, after it and at the 1st, 2nd and 3rd trimesters of pregnancy were 0.62 +/- 0.398, 0.88 +/- 0.106, 0.84 +/- 0.550, 1.25 +/- 0.834 and 0.67 +/- 0.413, respectively. The ratio at the 2nd trimester was significantly higher than that before the therapy (P < 0.05, paired t-test, n = 9). The results indicate that the immunosuppressive therapy affected the physiological balance between thromboxane A2 and prostacyclin, and improved clinical symptoms such as recurrent fetal wastage. PMID:9494925

  11. The Effects of Rm-CSF and Ril-6 Therapy on Immunosuppressed Antiorthostatically Suspended Mice

    NASA Technical Reports Server (NTRS)

    Armstong, Jason W.; Kirby-Dobbels, Kathy; Chapes, Steven K.

    1995-01-01

    Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of orthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.

  12. Melanoma in Immunosuppressed Patients

    PubMed Central

    Kubica, Agnieszka W.; Brewer, Jerry D.

    2012-01-01

    The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (≥1000 patients in organ transplant recipient studies; ≥500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients. PMID:23036673

  13. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    PubMed

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  14. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer

    PubMed Central

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385–0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  15. Intravenous immunoglobulin for treatment of severe acquired bullous epidermolysis refractory to conventional immunosuppressive therapy.

    PubMed

    Mosqueira, Carolina Balbi; Furlani, Laura de Albuquerque; Xavier, Augusto Frederico de Paula; Cunha, Paulo Rowilson; Galvão, Alda Maria Penna

    2010-01-01

    Acquired bullous epidermolysis is a chronic and rare bullous subepidermal disease. It usually begins in adulthood and its etiology is unknown although it is associated with antibodies against type VII collagen. There are spontaneous and trauma induced formation of blisters that may cause serious complications. Treatment is disappointing and difficult. Apart from conventional therapy with systemic corticosteroid, new therapeutic modalities such as intravenous immunoglobulin are currently being used. This report highlights the extremely difficult clinical management of this rare disease and the important improvement provided by intravenous immunoglobulin. PMID:20944913

  16. Immunosuppression for lung transplantation

    PubMed Central

    Ng, Choo Y.; Madsen, Joren C.; Rosengard, Bruce R.; Allan, James S.

    2010-01-01

    1. ABSTRACT As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients. PMID:19273152

  17. CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma

    PubMed Central

    Enblad, Gunilla; Karlsson, Hannah; Loskog, Angelica S.I.

    2015-01-01

    Chimeric antigen receptor (CAR) T-cells have shown remarkable results in patients with B-cell leukemia and lymphoma. However, while CAR T-cells have shown complete responses in a majority of patients with acute lymphoblastic leukemia (ALL), lymphomas are more difficult to treat. Different CAR designs and conditioning protocols seem to affect the persistence of patient responses. However, factors that determine if patients receiving the same CARs will respond or not remain obscure. In Sweden, a phase I/IIa trial using third-generation CAR T-cells is ongoing in which we intend to compare tumor biology and immunology, in each patient, to treatment response. CAR T-cell therapy is a powerful tool to add to the treatment options for this patient group but we need to perform the necessary basic research on the multifactorial mechanisms of action to give patients the best possible option of survival. Such studies are also crucial to expand the success of CAR T-cells beyond CD19+ B-cell malignancy. This review will focus on possible barriers of treating lymphoma to define factors that need to be investigated to develop the next generation of CAR T-cell therapy. PMID:26230974

  18. [Cost-effectiveness analysis of immunosuppressive drugs in post-renal transplantation maintenance therapy in adult patients in Brazil].

    PubMed

    Acurcio, Francisco de Assis; Saturnino, Luciana Tarbes Mattana; Silva, Anderson Lourenço da; Oliveira, Gustavo Laine Araújo de; Andrade, Eli Iola Gurgel; Cherchiglia, Mariangela Leal; Ceccato, Maria das Graças Braga

    2013-11-01

    The aim of the study was to perform cost-effectiveness analysis of immunosuppressive drugs in post-renal transplantation maintenance therapy. A hypothetical cohort of transplanted adults was followed for 20 years, using the Markov model. The 10 evaluated therapeutic regimens contained prednisone (P). Average cost of the medicines was obtained from CMED (Câmara de Regulação do Mercado de Medicamentos). Other patient care costs were included in each disease stage. Costs were expressed in Brazilian reais, effectiveness was measured as years of life gained, and the study adopted a public health system perspective. At the end of follow-up, the analysis with discount showed that all the regimens were dominated by cyclosporine (CSA)+azathioprine (AZA)+P. In the remaining analyses, tacrolimus+AZA+P was not dominated, but the incremental cost-effectiveness ratio between these two regimens was R$ 156,732.07/ years of life gained, a value that exceeds the threshold of three times the Brazilian per capita GDP. In the sensitivity analysis, no qualitative change was observed and the probability of CSA+AZA+P being the most cost-effective regimen was greater than 85%. PMID:25402255

  19. Renal Function and Proteinuria after Successful Immunosuppressive Therapies in Patients with FSGS

    PubMed Central

    Friedman, Aaron; Greene, Tom; Radeva, Milena; Budisavljevic, Milos N.; Gassman, Jennifer; Gipson, Debbie S.; Jefferson, J. Ashley; John, Eunice G.; Kaskel, Frederick J.; Moudgil, Asha; Moxey-Mims, Marva; Ortiz, Luis A.; Schelling, Jeffrey R.; Schnaper, William; Srivastava, Tarak; Trachtman, Howard; Vehaskari, V. Matti; Wong, Craig; Woronieki, Robert P.; Van Why, Scott K.; Zolotnitskaya, Anna

    2013-01-01

    Summary Background and objectives In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined. Design, setting, participants, and measurements The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2–40 years, with eGFR ≥40 ml/min per 1.73 m2 and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks. Results The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks. Conclusions In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR. PMID:23143503

  20. Negative effect of immunosuppressive therapy in the performance of the QuantiFERON gold in-tube test in patients with immune-mediated inflammatory diseases.

    PubMed

    Ramos, José M; Masiá, Mar; Rodríguez, Juan C; López, Cristina; Padilla, Sergio; Robledano, Catalina; Navarro-Blasco, Francisco J; Matarredona, Jaime; García-Sepulcre, Mariana F; Gutiérrez, Félix

    2013-08-01

    To compare the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFG) for the detection of latent tuberculosis infection among patients with immune-mediated inflammatory diseases before antitumor necrosis factor-α therapy. A prospective study including 153 consecutive patients with rheumatoid arthritis (n = 53), psoriasis (n = 45), inflammatory bowel disease (n = 25), and spondyloarthropathy (n = 22) were included. QFG and TST were performed simultaneously. TST was positive in 43/153 (28.1 %) patients. QFG (cutoff ≥ 0.35 IU/ml) was positive in 15/153 (9.8 %) patients, and indeterminate in one (0.7 %). QFG (cutoff ≥ 0.10 IU/ml) was positive in 25/153 (16.3 %). 59.5 % of the patients were on immunosuppressive therapy at the time of testing. There was a significant difference in the rate of positive QFG between patients with and without immunosuppressive therapy after adjustment for age and gender (cutoff ≥ 0.35 IU/ml, 4.6 vs. 17.4 %; adjusted odds ratio [AOR], 0.2; 95 % confidence interval [CI], 0.06-0.8; p = 0.03 and cutoff ≥ 0.10 IU/ml, 11.2 vs. 24.2 %; AOR, 0.3; 95 % CI, 0.1-0.93; p = 0.04). Agreement between TST and QFG was 'fair' (κ = 0.354 and κ = 0.365, for cutoffs ≥ 0.35 and ≥0.10 IU/ml, respectively). Among patients without immunosuppressive therapy, the concordance between TST and QFG was 'moderate-substantial' (κ = 0.593 and κ = 0.690, for cutoffs ≥ 0.35 IU/ml and ≥0.10 IU/ml, respectively). By contrast, among patients on immunosuppressive therapy the concordance was 'poor' (κ = 0.085; κ = 0.041, respectively). Immunosuppressive therapy affects negatively QFG performance. In patients with immune-mediated inflammatory diseases, QFG may have a limited role for screening of latent tuberculosis infection. PMID:22736247

  1. Costimulation-Adhesion Blockade is Superior to Cyclosporine A and Prednisone Immunosuppressive Therapy for Preventing Rejection of Differentiated Human Embryonic Stem Cells Following Transplantation

    PubMed Central

    Huber, Bruno C.; Ransohoff, Julia D.; Ransohoff, Katherine J.; Riegler, Johannes; Ebert, Antje; Kodo, Kazuki; Gong, Yongquan; Sanchez-Freire, Veronica; Dey, Devaveena; Kooreman, Nigel G.; Diecke, Sebastian; Zhang, Wendy Y.; Odegaard, Justin; Hu, Shijun; Gold, Joseph D.; Robbins, Robert C.; Wu, Joseph C.

    2014-01-01

    Rationale Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. Objective To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents. Methods and Results We transduced hESCs with a double fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), and differentiated these cells to endothelial cells (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell engraftment by bioluminescence imaging (BLI). Costimulation-adhesion therapy resulted in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in a hindlimb model. Costimulation-adhesion therapy also promoted robust hESC-EC and hESC-derived cardiomyocyte (hESC-CM) survival in an ischemic myocardial injury model. Improved hESC-EC engraftment had a cardioprotective effect after myocardial injury, as assessed by magnetic resonance imaging (MRI). Mechanistically, costimulation-adhesion therapy is associated with systemic and intra-graft upregulation of T cell immunoglobulin and mucin domain 3 (TIM3) and a reduced pro-inflammatory cytokine profile. Conclusions Costimulation-adhesion therapy is a superior alternative to current clinical immunosuppressive strategies for preventing the post-transplant rejection of hESC derivatives. By extending the window for cellular engraftment, costimulation-adhesion therapy enhances functional preservation following ischemic injury. This regimen may function through a TIM3-dependent mechanism. PMID:24038578

  2. The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.

    PubMed Central

    Elshami, A A; Kucharczuk, J C; Sterman, D H; Smythe, W R; Hwang, H C; Amin, K M; Litzky, L A; Albelda, S M; Kaiser, L R

    1995-01-01

    OBJECTIVE: To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. BACKGROUND DATA: Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. METHODS: After adenoviral transduction of a Fischer rat syngeneic mesothelioma cell line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. RESULTS: HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. CONCLUSION: These results indicate that the immune response against adenovirally transduced cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design. PMID:7677460

  3. SAFETY AND UTILITY OF ACUTE ELECTROCONVULSIVE THERAPY FOR AGITATION AND AGGRESSION IN DEMENTIA

    PubMed Central

    Acharya, Deepa; Harper, David G.; Achtyes, Eric D.; Seiner, Stephen J.; Mahdasian, Jack A.; Nykamp, Louis J.; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M.; Ujkaj, Manjola; Davidoff, Donald A.; Forester, Brent P.

    2015-01-01

    Objective Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Methods Twenty-three participants admitted to McLean Hospital (Belmont, MA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory (CMAI)-short form, Neuropsychiatric Inventory (NPI)-Nursing Home Version, Cornell Scale for Depression in Dementia (CSDD), and the Clinical Global Impression Scale (CGI) at baseline, during, and after the ECT course. Results Regression analyses revealed a significant decrease from baseline to discharge on the CMAI (F(4, 8) =13.3; p=0.006) and NPI (F(4, 31)= 14.6; p<0.001). There was no statistically significant change in scores on the CSDD. The CGI scores on average changed from a rating of “markedly agitated/aggressive” at baseline to “borderline agitated/aggressive” at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants due to recurrence of agitation and for three participants due to adverse events. Conclusions ECT may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. PMID:24838521

  4. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity.

    PubMed

    Shapiro, Roman; Chin-Yee, Ian; Lam, Selay

    2015-11-01

    Severe cold agglutinin disease with hemodynamic compromise requires rapid stabilization of the autoimmune hemolytic anemia as a bridge to the immunosuppressive effect of rituximab. Herein, we describe eculizumab treatment of severe complement-mediated hemolysis in a patient whose hemodynamic status deteriorated in spite of supportive blood transfusions and therapeutic plasma exchange. PMID:26576277

  5. Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression.

    PubMed

    Aron Badin, R; Vadori, M; Vanhove, B; Nerriere-Daguin, V; Naveilhan, P; Neveu, I; Jan, C; Lévèque, X; Venturi, E; Mermillod, P; Van Camp, N; Dollé, F; Guillermier, M; Denaro, L; Manara, R; Citton, V; Simioni, P; Zampieri, P; D'avella, D; Rubello, D; Fante, F; Boldrin, M; De Benedictis, G M; Cavicchioli, L; Sgarabotto, D; Plebani, M; Stefani, A L; Brachet, P; Blancho, G; Soulillou, J P; Hantraye, P; Cozzi, E

    2016-07-01

    Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation. PMID:26749114

  6. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  7. Photodynamic therapy in the treatment of aggressive periodontitis: A systematic review

    PubMed Central

    Doufexi, Aikaterini-Ellisavet

    2016-01-01

    Background Aggressive periodontitis (AgP) is a severe form of periodontal diseases with rapid destruction of the supporting bone around teeth. The efficacy of PDT in suppressing periodontal pathogens may be crucial in adopting new protocols for the treatment of AgP. Thus, the aim of this systematic review was to investigate the possible role of PDT in the treatment of AgP as an adjunctive therapy or monotherapy. Material and Methods A systematic search of the literature was performed. Additionally, the references from all the selected full-text studies were searched for relevant articles. Two reviewers screened independently titles and abstracts or full text copies. Quality assessment of all the included studies was held. Results Initial screening of electronic databases yielded 418 potentially relevant publications. After screening of the titles and full-text examination, five studies were included in the systematic review. Four publications evaluated the effects of PDT adjunctive to SRP in patients with AgP: two of them compared the clinical outcomes of SRP and PDT with a control group that received therapy with SRP and antibiotics (metronidazole and amoxicillin); two publications included SRP and PDT in the test group, and SRP alone in the control group. In one study, PDT was tested as a monotherapy compared with SRP alone. Conclusions Within the limitations of this review, PDT may exhibit a beneficial role in the therapy of aggressive periodontitis after repeated applications. In the future, more methodologically sound, long-term randomized clinical trials are needed to be conducted. Key words:Photodynamic therapy, periodontitis, systematic review. PMID:26595837

  8. Deoxyspergualin--a novel immunosuppressant.

    PubMed

    Jindal, R M; Tepper, M A; Soltys, K; Cho, S I

    1994-01-01

    DSG appears to have a unique, although as yet undefined, mechanism of action and may be a useful immunosuppressive agent. Because DSG is effective in reducing preformed antibodies in the xenograft situation, it may have a significant advantage in ABO-incompatible grafts in transplant recipients with high panel-reactive antibodies. Most important, DSG may have a definitive role in immunosuppressive therapy for pancreatic grafts. PMID:8183294

  9. Long-term remission of pulmonary veno-occlusive disease associated with primary Sjögren's syndrome following immunosuppressive therapy.

    PubMed

    Naniwa, Taio; Takeda, Yutaka

    2011-12-01

    The patient described here is a 21-year-old Japanese woman with primary Sjögren's syndrome (pSS) presenting with worsening of dyspnea, palpitation, recurrent parotitis, and arthritis. Chest computed tomography showed diffuse interlobular septal thickening and ground-glass opacities. Right heart catheterization demonstrated pulmonary hypertension, right-sided heart failure, normal pulmonary capillary wedge pressure, and no evidence of arterio-venous shunt. Transbronchial lung biopsy showed luminal obliteration of pulmonary venules by intimal cellular proliferations, without abnormalities in the small pulmonary arteries. These findings were consistent with pulmonary veno-occlusive disease (PVOD). Immunosuppressive therapy, starting with prednisolone 20 mg/day and subsequently combined with azathioprine, resulted in the disappearance of the signs and symptoms, including exertional dyspnea and abnormal pulmonary parenchymal shadows on computed tomography, and the normalization of pulmonary artery pressure. So far, there have been no reported cases of PVOD associated with pSS. Of interest, immunosuppressive therapy without vasodilator therapy almost completely resolved the pulmonary hypertension in this patient. PMID:21394665

  10. Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

    2005-01-01

    This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  11. Maintenance therapy with interferon-alpha 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Castañeda, Claudia; Talavera, Alejandra; Huerta-Guzmán, Judith; Murillo, Edgar

    2004-04-01

    Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy. PMID:15186737

  12. [A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].

    PubMed

    Matsuse, Hiroto; Oshio, Takeshi; Kishimoto, Kumiko; Nakayama, Haruo

    2016-02-01

    A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases. PMID:27263226

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

    PubMed Central

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

    2016-01-01

    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 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. Conclusion This study provides qualitative evidence about the barriers to IT

  14. Everolimus in combination with cyclosporin a as pre- and posttransplantation immunosuppressive therapy in nonmyeloablative allogeneic hematopoietic stem cell transplantation.

    PubMed

    Junghanss, Christian; Rathsack, Susanne; Wacke, Rainer; Weirich, Volker; Vogel, Heike; Drewelow, Bernd; Mueller, Sabrina; Altmann, Simone; Freund, Mathias; Lange, Sandra

    2012-07-01

    Everolimus (RAD001) is an mTOR inhibitor that has been successfully used as an immunosuppressant in solid-organ transplantation. Data in allogeneic hematopoietic stem cell transplantation (HSCT) is limited. This study aimed to investigate pharmacokinetics, safety, and efficacy of RAD001 in a canine allogeneic HSCT model. First, pharmacokinetics of RAD001 were performed in healthy dogs in order to determine the appropriate dosing. Doses of 0.25 mg RAD001 twice daily in combination with 15 mg/kg cyclosporin A (CsA) twice daily were identified as appropriate starting doses to achieve the targeted range of RAD001 (3-8 μg/L) when orally administered. Subsequently, 10 dogs were transplanted using 2 Gy total body irradiation (TBI) for conditioning and 0.25 mg RAD001 twice daily plus 15 mg/kg CsA twice daily for pre- and posttransplantation immunosuppression. Seven of the 10 transplanted dogs were maintained at the starting RAD001 dose throughout the study. For the remaining 3 dogs, dose adjustments were necessary. RAD001 accumulation over time did not occur. All dogs initially engrafted. Five dogs eventually rejected the graft (weeks 10, 10, 13, 27, and 56). Two dogs died of pneumonia (weeks 8 and 72) but were chimeric until then. Total cholesterol rose from median 4.1 mmol/L (3.5-5.7 mmol/L) before HSCT to 6.0 mmol/l (5.0-8.5 mmol/l) at day 21 after HSCT, but remained always within normal range. Changes in creatinine and triglyceride values were not observed. Long-term engraftment rates were inferior to sirolimus/CsA and mycophenolate mofetil (MMF)/CsA regimen, respectively. RAD001/CsA caused a more pronounced reduction of platelet counts to median 2 × 10(9)/L (range: 0-21 × 10(9)/L) and longer time to platelet recovery of 21 days (range: 14-24 days) compared with MMF/CsA. CsA c(2h) levels were significantly enhanced in the RAD001/CsA regimen, but c(0h) and area under the curve from 0 to 12 hours (AUC(0-12h)) values did not differ compared with an MMF

  15. Unusually Aggressive Primary Testicular Diffuse Large B Cell Lymphoma with Post Therapy Extensive Metastasis

    PubMed Central

    Goel, Shalini; Mohapatra, Ishani; Gajendra, Smeeta; Gupta, Sunil

    2016-01-01

    Primary Testicular Lymphoma (PTL) is a rare intermediate to high grade tumour, diffuse large cell being the most common type. Unlike nodal Diffuse Large B-Cell Lymphoma (DLBCL), testicular DLBCL has a less aggressive course and better prognosis. Metastasis is uncommon in testicular DLBCL. Commonly involved sites are contralateral testes, Waldeyer’s ring, skin, lung, Central Nervous System (CNS) and prostate, however the kidneys, liver, bone marrow, pleura and bones are more rarely involved. We report a case of testicular DLBCL which has metastasized to skin and bone marrow with an aggressive clinical course in a year, in-spite of combined modality of therapy given to the patient. Bone marrow infiltration is common and well documented with nodal DLBCL, however there is no published literature for simultaneous bone marrow and skin infiltration in testicular DLBCL till date. Other large studies done in the west have shown that distinct metastasis is usually common but the median progression-free survival is usually in years. This case stresses on shorter period of progression after standard treatment protocol in this part of the world, thus highlighting the need for other extensive studies to define specific treatment protocol for testicular DLBCL.

  16. Which Patients With Mantle Cell Lymphoma Do Not Need Aggressive Therapy.

    PubMed

    Ruan, Jia; Martin, Peter

    2016-06-01

    Mantle cell lymphoma (MCL) is a heterogeneous disease, and it has been well-established over the last decade that a subset of patients can have indolent presentation. It is therefore important to adopt a risk-stratified approach in order to minimize unnecessary toxicities while maximizing survival and quality of life in selected MCL patients. This review provides an up-to-date assessment of clinical and pathologic entities associated with indolent disease course and delineates available biomarkers with predictive significance. Initial treatment decisions should be guided by risk assessment to discern patients who might do well with deferred therapy, from those who would require treatment with non-aggressive first-line regimens. PMID:27068437

  17. Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) in Reducing Aggression of Individuals at the Juvenile Correction and Rehabilitation Center

    PubMed Central

    Milani, Atefeh; Nikmanesh, Zahra; Farnam, Ali

    2013-01-01

    Background: In the present era, delinquency in children and adolescents is undoubtedly a difficult and upsetting issue attracting the attention of many experts such as psychologists, sociologists, and criminologists. These experts often try to answer why a number of children and adolescents engage in various crimes such as aggressive and anti-social crimes. They also try to find out how these crimes can be prevented. Objectives: The present study investigates the effectiveness of mindfulness-based cognitive therapy training (MBCT) in reducing aggression in a juvenile correction and rehabilitation center of Zahedan province during years 1991 to 1992. Materials and Methods: This experimental study included an experimental and a control group with a pretest, posttest, and follow-up approach. The Buss and Perry aggression questionnaire (1992) was used for data collection. The sample group included 22 (10 experimental and 12 control groups) adolescent males in a juvenile correction and rehabilitation center of Zahedan province who were selected through a census method. Using a matching method based on the pre-test scores of the aggression questionnaire, they were then divided into two equivalent categories and were randomly assigned to the two groups. Mindfulness-based cognitive training took the group training in 8 sessions administered on experimental group. The follow-up test was conducted two weeks after the end of the posttest sessions. The results were analyzed using ANCOVA. Results: The results of ANCOVA showed that mindfulness-based cognitive training could significantly reduce aggression during posttest and follow-up test phases in the experimental group, compared to the control group (P < 0.01). Moreover, the results indicated the effectiveness of this method in significantly reducing anger, physical aggression, and hostility during posttest and follow-up test phases (P < 0.05). However, no significant reduction was observed in the verbal aggression subscale

  18. A Simplified HAART Regimen with Raltegravir and Lamivudine, and Pharmacokinetic Interactions with a Combined Immunosuppressive Therapy with Tacrolimus and Everolimus in an HIV/HCV/HBV/HDV Patient after Liver Transplantation

    PubMed Central

    Cirioni, O; Weimer, LE; Fragola, V; Giacometti, A; Ancarani, F; Maracci, M; Gabrielli, E; Marchionni, E; Pirillo, MF; Vella, S

    2014-01-01

    ABSTRACT In this case report, we examine the impact of a simplified two-drug highly active antiretroviral therapy (HAART) regimen of raltegravir and lamivudine in a patient co-infected with human immunodeficiency virus (HIV) and hepatitis C, D and B viruses (HCV/HDV/HBV) under immunosuppressive therapy after liver transplantation. Pharmacokinetic interactions between integrase inhibitors and immunosuppressant drugs are described. Raltegravir, the first integrase inhibitor, associated with lamivudine, was introduced because its metabolism does not interfere with immunosuppressant therapy. During post-orthotopic liver transplantation follow-up, the patient's transaminases level increased and his antiretroviral therapy (HAART) of tenofovir/emtricitabine and fosamprenavir was changed, due to suspected drug toxicity. After seven months of follow-up, the patient showed good tolerance, good viro-immunological control with undetectable HIV viraemia and stable concentrations of immunosuppressive drugs. This case indicates that the combination of raltegravir and lamivudine is an optimal and effective strategy because it resulted in an important reduction of hepatic transaminases in a patient with very critical clinical conditions. PMID:25867565

  19. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  20. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas. PMID:24287797

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

    PubMed Central

    Javaid, Muhammad M; Denley, Helen; Tagboto, Senyo

    2007-01-01

    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. PMID:17490479

  2. Ethanol immunosuppression in vitro

    SciTech Connect

    Kaplan, D.R.

    1986-03-01

    Ethanol in concentrations equivalent to levels achieved by the ingestion of moderate to large amounts of alcoholic beverages has been shown to inhibit mitogen and anti-CD3 stimulated human T lymphocyte proliferation. This inhibition was monophasic suggesting that ethanol affected a single limiting component of T cell proliferation. In experiments designed to test the effect of ethanol on various aspects of proliferation, it was demonstrated that ethanol inhibited the capacity of exogenously supplied interleukin 2 to stimulate proliferation of T cells that had previously acquired interleukin 2 receptors in a monophasic, dose-dependent manner. Moreover, there was no suppression of interleukin 2 production or interleukin 2 receptor acquisition. Thus, ethanol was shown to mediate immunosuppression by a mechanism specific to one component of proliferation. Additive inhibition of T cell proliferation was seen with ethanol plus cyclosporin A which inhibits interleukin 2 production. The level of inhibition with 250 ng/ml cyclosporin A alone was equivalent to the level seen with 62 ng/ml cyclosporin A plus 20 mM (94 mg%) ethanol. Ethanol also suppressed an immune effector mechanism. NK cytotoxicity was depressed in a monophasic, dose-dependent manner. Thus, ethanol might be considered as a possible adjunct in immunosuppressive therapy.

  3. New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression

    PubMed Central

    Steward-Tharp, Scott M.; Song, Yun-jeong; Siegel, Richard M.; O'Shea, John J.

    2010-01-01

    T cell-directed therapies have become mainstays in the management of various autoimmune diseases and organ transplantation. The understanding of T cell biology has expanded greatly since the development of most agents currently in use. Here we discuss important recent discoveries pertaining to T helper cell differentiation, lineage commitment, and function. Within this context, we examine existing T cell-directed therapies, including new agents being evaluated in clinical and preclinical studies. We also use recent findings to speculate on novel targets. PMID:20146712

  4. Antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: a systematic review and meta-analysis.

    PubMed

    Souza, Emmanuel; Medeiros, Ana Cláudia; Gurgel, Bruno César; Sarmento, Carlos

    2016-01-01

    The aim of this systematic review was to investigate whether the use of antimicrobial photodynamic therapy (aPDT) as an adjuvant to scaling and root planning (SRP) yields better results than SRP alone or associated with systemic antibiotics in the treatment of aggressive periodontitis (AgP). A meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements and Cochrane Collaboration recommendations. The search for relevant studies (earliest record to January 2015) was carried out in seven databases, followed by a manual search. Methodological quality assessment of the studies selected was based on an analysis of the risk of bias. At each time point of follow-up, the existence of significant differences (p < 0.05) in clinical attachment level (CAL) gain and probing depth (PD) reduction (primary outcomes) between groups was assessed with RevMan software 5.0. Heterogeneity between studies was assessed by the Higgin test (I (2)). Four randomized controlled trials (RCTs) satisfied the eligibility criteria of this review. Only one study was found to have a low risk of bias. There were no significant differences in PD reduction (mean difference 0.33, 95 % confidence interval -0.32 to 0.98, p = 0.32) and CAL gain (mean difference 0.20, 95 % confidence interval -0.41 to 0.81, p = 0.53) between the test and control interventions. At present, therefore, when compared to SRP alone or associated with systemic antibiotics, the evidence suggests that the association of aPDT + SRP is of no additional benefit in the nonsurgical treatment of AgP. PMID:26563956

  5. Maintenance periodontal therapy after systemic antibiotic and regenerative therapy of generalized aggressive periodontitis. A case report with 10-year follow-up.

    PubMed

    Siqueira, Sergio Júnior; Ribeiro, Fernanda Vieira; Villalpando, Karina Teixeira; Cirano, Fabiano Ribeiro; Pimentel, Suzana Peres

    2015-05-01

    Aggressive periodontitis (AgP) is an inflammatory disease characterized by rapid attachment loss and bone destruction. This case report presents the 10-year results in a subject with generalized AgP treated by a regenerative periodontal therapeutic approach and the adjunctive use of antibiotics, following a systematic maintenance periodontal therapy. The use of enamel matrix derivatives (EMD) and adjunctive antibiotic therapy to treat AgP yielded improvements in clinical parameters and radiographic bony fill. This combined therapeutic approach following a systematic supportive periodontal therapy supports the long-term maintenance of teeth with previous advanced periodontal defects, demonstrating successful stability after 10-years follow-up. Clinical Relevance: The combined treatment protocol using EMD plus adjunctive antibiotic therapy, associated with a systematic supportive periodontal therapy, benefits the long-term maintenance of teeth with previous advanced periodontal defects in subjects presenting AgP, supporting this approach as an alternative in the treatment of AgP. PMID:26062264

  6. Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia

    PubMed Central

    Shih, Chia-Jen; Tarng, Der-Cherng; Yang, Wu-Chang; Yang, Chih-Yu

    2014-01-01

    INTRODUCTION Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life-threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. METHODS From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. RESULTS Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01–3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. CONCLUSION In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature. PMID:25091886

  7. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report

    PubMed Central

    UMEDA, KATSUTSUGU; SAIDA, SATOSHI; YAMAGUCHI, HIDEKI; OKAMOTO, SHINYA; OKAMOTO, TAKESHI; KATO, ITARU; HIRAMATSU, HIDEFUMI; IMAI, TSUYOSHI; KODAIRA, TAKESHI; HEIKE, TOSHIO; ADACHI, SOUICHI; WATANABE, KEN-ICHIRO

    2016-01-01

    Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID:26870296

  8. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  9. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  10. The Rosenzweig Picture-Frustration Study "Extra-Aggression" Score as an Indicator in Cognitive Restructuring Therapy for Male Perpetrators of Domestic Violence

    ERIC Educational Resources Information Center

    Norman, Michael; Ryan, Lawrence J.

    2008-01-01

    It was hypothesized that male perpetrators of domestic violence in the early stages of a 1-year process of cognitive restructuring therapy would manifest on the Rosenzweig Picture-Frustration Study higher levels of extra-aggressiveness than in later stages of the therapy process. A sample of male batterers in the process of treatment took the…

  11. Cognitive behavioral therapy to reduce overt aggression behavior in Chinese young male violent offenders.

    PubMed

    Chen, Chen; Li, Chun; Wang, Hong; Ou, Jian-Jun; Zhou, Jian-Song; Wang, Xiao-Ping

    2014-01-01

    This 9-week study was designed to determine whether a commercial cognitive-behavioral training program could effectively reduce overt aggression behavior in Chinese young male violent offenders. Sixty-six participants were randomly assigned to receive routine intervention alone (control group) or routine intervention plus Williams LifeSkills Training (WLST group) in a 1:1 ratio. The primary outcome was change scores on the Modified Overt Aggression Scale (MOAS) from baseline to one week following end of training. Secondary outcomes were change scores on the Barratt Impulsiveness Scale-11 (BIS-11) and Cook-Medley Hostility Scale (CMHS). There were significant between-group differences in change of MOAS total score (P < .001) and all sub-scores (Ps < .01) except aggression against property. Between-group differences were also observed in change of BIS-11 and CMHS total score (Ps < 0.05). All results favored the WLST group. These findings suggest WLST has the potential to be an effective intervention to reduce overt aggressive behavior in young male violent offenders. PMID:24375428

  12. Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function

    PubMed Central

    McGregor, JulieAnne G.; Negrete-Lopez, Roberto; Poulton, Caroline J.; Kidd, Jason M.; Katsanos, Suzanne L.; Goetz, Lindsey; Hu, Yichun; Nachman, Patrick H.; Falk, Ronald J.; Hogan, Susan L.

    2015-01-01

    Background Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV. Methods Biopsy-proven AAV patients (diagnosed 1/1991–6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1–2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals. Results A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1–2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0–8.7; P = 0.001). Conclusions More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity. PMID:25805747

  13. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs. PMID:22149431

  14. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

    PubMed Central

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  15. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

    PubMed

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L; Shea, Thomas C; Liomba, N George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  16. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    SciTech Connect

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter

  17. Dialectical behavior therapy deployed: an aggressive alternative to traditional mental health on the noncontiguous battlefield.

    PubMed

    Parrish, Brian D

    2008-01-01

    This paper provides a description of the Witmer Wellness Center, the first successful military application of dialectical behavior therapy in a theater of war. Dialectical behavior therapy is a dynamic and provocative evidenced-based modification of cognitive behavioral treatment developed by Dr Marsha Linehan for patients with severe emotional dysregulation. One of the primary concepts of dialectical behavior therapy is that self-harming behaviors are learned, and provide evidence of maladaptive coping that is reinforced in an invalidating environment. Dialectical behavior therapy recommends a hierarchy of goals to effectively address the behaviors associated with dysregulation. Chief among these goals is reducing risk of violence to self or others. Dialectical behavior therapy is especially well-suited for the complex and dynamic environment of the noncontiguous battlefield with its chronic threat of ultraviolence, strain of nonresponse, shifting rules of engagement, and extended duration and frequency of combat deployments. The Witmer Wellness Center program uses an intensive outpatient organizational structure and minimal, but innovative, modifications to standard dialectical behavior therapy designed to meet the special requirements of Warriors in a combat zone. The Wellness Center program was designed and implemented during Operation Iraqi Freedom 07-09, at a time during the troop surge when suicide rates among US forces had reached an unprecedented level. PMID:20088061

  18. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  19. Treatment of inflammatory myopathy: emerging therapies and therapeutic targets

    PubMed Central

    Moghadam-Kia, Siamak; Aggarwal, Rohit; Oddis, Chester V

    2016-01-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy and myositis-associated interstitial lung disease. Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. First-line conventional immunosuppressive drugs include either methotrexate or azathioprine, and when they fail, more aggressive therapy includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous immunoglobulin, rituximab, or cyclophosphamide, used alone or in various combinations. Further investigations are required to assess the role of more novel therapies in the treatment of myositis and myositis-associated interstitial lung disease. PMID:26313852

  20. Identification of targeted therapy for an aggressive subgroup of muscle-invasive bladder cancers.

    PubMed

    Lebret, Thierry; Neuzillet, Yann; Houede, Nadine; Rebouissou, Sandra; Bernard-Pierrot, Isabelle; De Reynies, Aurélien; Benhamou, Simone; Allory, Yves; Radvanyi, François

    2015-01-01

    Rebouissou et al. recently provided preclinical evidence that a subset of patients with muscle-invasive bladder cancer might benefit from anti-epidermal growth factor receptor (EGFR) therapy and reported diagnostic tools for identifying these patients in the clinical setting. This work also identified relevant experimental models that may be useful for future basic and clinical research on this subgroup of tumors. PMID:27308521

  1. Immunosuppression during spaceflight deconditioning.

    PubMed

    Levine, D S; Greenleaf, J E

    1998-02-01

    Spaceflight results in immunosuppression which is likely due mainly to neurohumoral factors released in response to intermittent stress effects during flight. However, no major non-physiological health problems have been reported during or following spaceflight, but diseases resulting from immunosuppression could occur on long-duration missions and would include bacterial, fungal, and viral infections in addition to increased incidence of neoplasia and autoimmunity. Pharmacokinetics and pharmacodynamics appear to be altered during spaceflight and, as a consequence, alternative drug administration and dosing procedures will need to be developed. Moderate exercise training enhances immune function, but in-flight exercise may affect immunological parameters and immunity in ways not yet ascertained. Hyperosmolality may enhance some immune parameters, and attenuate others especially when associated with dehydration and exercise. Reducing in-flight stress may attenuate flight-induced immunosuppression, but pharmacological interventions may be essential to prevent undesirable immune responses which may occur on long-duration missions to Mars. PMID:9491259

  2. How do we manage high-grade T1 bladder cancer? Conservative or aggressive therapy?

    PubMed Central

    Kim, Seon-Kyu; Kim, Wun-Jae

    2016-01-01

    High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. PMID:27326407

  3. The Relationship Between the Level of Program Integrity and Pre- and Post-Test Changes of Responsive-Aggression Regulation Therapy (Re-ART) Outpatient: A Pilot Study.

    PubMed

    Hoogsteder, Larissa M; van Horn, Joan E; Stams, Geert Jan J M; Wissink, Inge B; Hendriks, Jan

    2016-03-01

    Responsive-Aggression Regulation Therapy (Re-ART) Outpatient is a cognitive behavioral-based intervention for adolescents and young adults (16-24 years) with severe aggressive behavioral problems. This pilot study (N = 26) examined the level of program integrity (PI; that is, the delivery of the intervention as it is originally intended) of Re-ART. We also investigated the pre- and post-test changes in several outcome variables, and the relation between the level of PI and these changes. Participants were recruited from three different outpatient forensic settings. Results showed that the PI of half of the treatments was not sufficient (e.g., the intensity of the program was too low and some standard modules were not offered). In addition, this pilot study demonstrated that sufficient PI was related to positive changes in aggression, cognitive distortions, social support, coping (reported by therapist), and distrust (responsiveness to treatment). PMID:25326466

  4. Immunosuppression During Trypanosomiasis

    PubMed Central

    Goodwin, L. G.; Green, D. G.; Guy, M. W.; Voller, A.

    1972-01-01

    Mice and rabbits infected with Trypanosoma brucei developed much lower agglutinin levels than uninfected animals when injected with sheep erythrocytes. The immunosuppression became more marked as the infection progressed. The infected rabbits produced heterophile agglutinins but the mice did not. PMID:5014242

  5. Immunosuppressive plasma cells impede T cell-dependent immunogenic chemotherapy

    PubMed Central

    Shalapour, Shabnam; Font-Burgada, Joan; Di Caro, Giuseppe; Zhong, Zhenyu; Sanchez-Lopez, Elsa; Dhar, Debanjan; Willimsky, Gerald; Ammirante, Massimo; Strasner, Amy; Hansel, Donna E.; Jamieson, Christina; Kane, Christopher J.; Klatte, Tobias; Birner, Peter; Kenner, Lukas; Karin, Michael

    2015-01-01

    Cancer-associated genetic alterations induce expression of tumor antigens which can activate CD8+ cytotoxic T cells (CTL), but the microenvironment of established tumors promotes immune tolerance through poorly understood mechanisms1,2. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumor-directed CTL and are effective in some human cancers1. Immune mechanisms also affect treatment outcome and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death (ICD) and other effector mechanisms3,4. Our previous studies revealed that B lymphocytes recruited by CXCL13 into prostate cancer (PC) promote castrate-resistant PC (CRPC) by producing lymphotoxin (LT) which activates an IKKα-Bmi1 module in PC stem cells5,6. Since CRPC is refractory to most therapies, we examined B cell involvement in acquisition of chemotherapy resistance. We focused this study on oxaliplatin, an immunogenic chemotherapeutic3,4 that is effective in aggressive PC7. We found that B cells modulate the response to low dose oxaliplatin, which by inducing ICD promotes tumor-directed CTL activation. Three different mouse PC models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The critical immunosuppressive B cells are plasmocytes that express IgA, IL-10 and PD-L1, whose appearance depends on TGFβ-receptor (TGFβR) signaling. Elimination of these cells, which also infiltrate human therapy-resistant PC, allows CTL-dependent eradication of oxaliplatin-treated tumors. PMID:25924065

  6. Immunosuppressive drugs and fertility.

    PubMed

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. PMID:26490561

  7. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  8. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  9. The Effects of Aggression on Symptom Severity and Treatment Response in a Trial of Cognitive Behavioral Therapy for Panic Disorder

    PubMed Central

    Cassiello-Robbins, Clair; Conklin, Laren R.; Anakwenze, Ujunwa; Gorman, Jack M.; Woods, Scott W.; Shear, M. Katherine; Barlow, David H.

    2015-01-01

    Background Previous research suggests that patients with panic disorder exhibit higher levels of aggression than patients with other anxiety disorders. This aggression is associated with more severe symptomatology and interpersonal problems. However, few studies have examined whether higher levels of aggression are associated with a worse treatment response in this population. Methods The present study sought to examine the association of aggression with panic disorder symptom severity in a sample of 379 patients who participated in a trial examining long-term strategies for the treatment of panic disorder. Results We found that aggression was significantly associated with higher baseline levels of panic disorder symptoms, anxiety, depression, and functional impairment. Further, we found that patients higher in aggression did not achieve the same level of improvement in general anxiety symptoms during treatment compared to patients lower in aggression, even when controlling for baseline anxiety symptom severity. Conclusion These results suggest that more research is needed concerning patients with anxiety disorders with higher aggression, as they may be a group in need of additional treatment considerations. PMID:25987198

  10. Efficacy of Photodynamic Therapy and Lasers as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis – A Clinical and Microbiologic Short Term Study

    PubMed Central

    Sarkar, Indranil; Rajan, Padma; Pai, Jagdish; Malagi, Sachin; Bharmappa, Radhika; Kamath, Vinesh

    2016-01-01

    Introduction Aggressive periodontitis comprises a group of rare, severe, rapidly progressive form of periodontitis. Conventional treatment includes mechanical debridement augmented with adjunctive antimicrobial therapy. Development of antibiotic resistance has led to use of lasers. Photodynamic therapy (PDT) is a novel non-invasive therapeutic approach with increased site and pathogen specificity. This study compares PDT and Lasers as an adjunct to conventional Scaling in the treatment of patients with aggressive periodontitis. Materials and Methods Fifteen untreated aggressive periodo-ntitis patients were randomly assigned in a split mouth design for one of the following treatment modalities: 1) SRP alone; (2) SRP + Diode Laser irradiation with 810 nm at 1W, continuous mode for 30 sec per tooth; (3) SRP + PDT on “0” day; (4) SRP + PDT on “0”, 7th and 21st day. The clinical parameters included PI, BOP, PPD, CAL recorded at the baseline & 3rd month. The site with greatest probing pocket depth (PPD) was selected from each quadrant for bacterial sampling and cultured for Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis & Prevotella intermedia. Results Statistically significant reduction in clinical & microbial parameters was seen. Sites 4 showed a greater reduction compared to other groups. Conclusion Photodynamic therapy is a valuable treatment modality adjunctive to conventional scaling and root planing. PMID:27042576

  11. An echo-guided case report of rapid regression of unstable mobile thrombus aortic atheroma after aggressive statin and antiplatelet combination therapy.

    PubMed

    Dʼaloia, Antonio; Vizzardi, Enrico; Caretta, Giorgio; Zanini, Gregoriana; Bugatti, Silvia; Curnis, Antonio; Dei Cas, Livio

    2014-01-01

    We describe a case report that documented the efficacy and safety of medical therapy in stabilizing and resolving a complex and unstable aortic atheroma after a relatively short period. The patient had a large protruding, mobile, calcified nonulcerated atheroma involving the descending aorta and was therefore treated with aggressive combination therapy with high statin dosages (atorvastatin = 80 mg) and dual antiplatelet treatment (clopidogrel = 75 mg and aspirin = 100 mg). At follow-up, the echocardiogram showed a significant regression in the atheroma volume, with no signs suggestive of ulceration on its surface with the complete mobile component resolution. PMID:23817345

  12. BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

    PubMed

    Zheng, Hua-chuan; Li, Jing; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Wu, Ya-zhou; Takano, Yasuo; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Gou, Wen-feng

    2015-08-14

    Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer. PMID:26050197

  13. Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.

    PubMed

    Chessells, J M; Durrant, J; Hardy, R M; Richards, S

    1986-12-01

    The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival

  14. Catastrophic gastrointestinal complication of systemic immunosuppression.

    PubMed

    Smith, Lyn Alexandra; Gangopadhyay, Mitali; Gaya, Daniel R

    2015-02-28

    We present a case of acute upper gastrointestinal haemorrhage in a patient with systemic vasculitis immunosuppressed on cyclophosphamide and prednisolone. The patient presented with a diffuse haemorrhagic oesophagitis and a non-specific duodenitis. Biopsies taken from the oesophagus and duodenum demonstrated infection with herpes simplex virus (HSV) and cytomegalovirus (CMV) respectively. Viral infection of the upper gastrointestinal tract is a recognised complication of immunosuppression and HSV is one of the most common pathogens. CMV on the other hand most commonly causes a colitis or less commonly oesophagitis. CMV enteritis is rare as is the synchronous infection with two viral agents in an immunocompromised patient having being described in a few case series only. Viral infection of the gastrointestinal tract in immunocompromised patients should be treated with systemic anti-viral medication and consideration to withdrawal of the immunosuppressive therapy if possible and appropriate. The authors highlight the need for a high suspicion of viral infection in immunosuppressed patients presenting with upper gastrointestinal bleeding. PMID:25741165

  15. Tilting toward immunosuppression

    PubMed Central

    Hotchkiss, Richard S.; Coopersmith, Craig M.; McDunn, Jonathan E.; Ferguson, Thomas A.

    2013-01-01

    The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease. PMID:19424209

  16. New approaches for immunosuppression

    SciTech Connect

    Eiseman, B.; Hansbrough, J.; Weil, R.

    1980-01-01

    New approaches for experimental immunosuppression have been reviewed. These include the following: (1) cyclosporin A, a metabolite from fungus that suppresses multiplying but not resting T and B lymphocytes and can be used in pulsed manner with interspersed drug-free periods; (2) total lymphoid irradiation (transplantation tolerance in rats has been achieved by pretransplant radiation); (3) thoracic duct drainage, which is being revived following its demonstrated effectiveness in the treatment of some autoimmune diseases; (4) hyperbaric oxygen (HBOX). We have found that HBOX 2 1/2 ATA for five hours daily depresses cell-mediated immunity in mice and that this can be reversed by intravenous administration of autologous macrophages.

  17. Clinical Factors Influencing the Efficacy of Systemic Moxifloxacin in the Therapy of Patients With Generalized Aggressive Periodontitis: A Multilevel Analysis From a Clinical Trial

    PubMed Central

    Ardila, Carlos M.; Guzmán, Isabel C.

    2016-01-01

    Background: It has been reported that clinical results of mechanical periodontal treatment could differ between subjects and among different sites of the tooth in the patient. The objective of this multilevel analysis is to investigate clinical factors at subject and sites of the tooth that influence variations in clinical attachment (CAL) increase and probing depth (PD) diminution of adjunctive moxifloxacin (MOX) at six months post-treatment in generalized aggressive periodontitis. Methods: This clinical trial included 40 patients randomly distributed to two therapy protocols: scaling and root planing alone or combined with MOX. Multilevel linear models for continuous variables were formulated to evaluate the clinical impact of the hierarchical configuration of periodontal data. Results: Six months following therapy, the divergences between both protocols were statistically significant in PD diminution and CAL increase, favouring the MOX therapy (p<0.001). Besides, the multilevel analysis revealed that adjunctive MOX at the subject level, non-molar and the interaction non-molar x MOX at the tooth level, interproximal sites and the interaction interproximal sites x MOX at the site level, were statistically significant factors in determining CAL increase and PD diminution. Conclusions: The main cause of variability in CAL gain and PD reduction following adjunctive MOX was attributable to the tooth level. Adjunctive MOX and their interactions with non-molar and interproximal sites showed higher clinical benefits at the tooth and site levels which could be essential for PD reduction and CAL gain in generalized aggressive periodontitis subjects. PMID:26493435

  18. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  19. Neurobehavioral consequences of small molecule-drug immunosuppression.

    PubMed

    Bösche, Katharina; Weissenborn, Karin; Christians, Uwe; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Hadamitzky, Martin

    2015-09-01

    60 years after the first successful kidney transplantation in humans, transplant patients have decent survival rates owing to a broad spectrum of immunosuppressive medication available today. Not only transplant patients, but also patients with inflammatory autoimmune diseases or cancer benefit from these life-saving immunosuppressive and anti-proliferative medications. However, this success is gained with the disadvantage of neuropsychological disturbances and mental health problems such as depression, anxiety and impaired quality of life after long-term treatment with immunosuppressive drugs. So far, surprisingly little is known about unwanted neuropsychological side effects of immunosuppressants and anti-proliferative drugs from the group of so called small molecule-drugs. This is partly due to the fact that it is difficult to disentangle whether and to what extent the observed neuropsychiatric disturbances are a direct result of the patient's medical history or of the immunosuppressive treatment. Thus, here we summarize experimental as well as clinical data of mammalian and human studies, with the focus on selected small-molecule drugs that are frequently employed in solid organ transplantation, autoimmune disorders or cancer therapy and their effects on neuropsychological functions, mood, and behavior. These data reveal the necessity to develop immunosuppressive and anti-proliferative drugs inducing fewer or no unwanted neuropsychological side effects, thereby increasing the quality of life in patients requiring long term immunosuppressive treatment. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. PMID:25529273

  20. Circulating antibodies against bacterial wall products: are there arguments for early immunosuppression?

    PubMed

    Rieder, Florian; Kugathasan, Subra

    2012-01-01

    The disease course of inflammatory bowel disease (IBD) is highly heterogeneous and unpredictable. The risk of fistulae formation and stricturing complications that lead to surgery during the disease course is substantial. Use of early and aggressive immunosupressive therapies such as immunomodulation could have the potential for altering the natural history of IBD, namely reducing the number of hospitalizations and surgeries. If diagnostic tools are available to predict disease activity, response to therapy, disease complications as well as the need for surgery or hospitalizations, one could identify IBD patients at risk that might benefit from more intense immunosuppression. Circulating antibodies against bacterial wall products, such as anti-Saccharomyces cervisiae antibodies have been investigated for the diagnosis and disease stratification of IBD. These markers are mainly linked to Crohn's disease (CD), are associated with genetic polymorphisms such as NOD2, and are linked to and possibly predictive of complicated CD behavior and CD-related surgery. No association of these antibodies has been found on assessment of disease activity, tissue healing or surgical recurrence. Perinuclear antineutrophil cytoplasmic antibodies are linked to ulcerative colitis (UC) and are associated with a severe UC disease course, the need for surgery and (potentially) the response to therapy, but not disease activity. Serological antimicrobial antibodies are promising tools for the identification and prediction of risk for the development of complicated disease during the disease course in CD. To truly improve daily clinical practice serological antimicrobial antibodies need to be incorporated into clinical therapeutic trials to assess their role in identifying patients who may benefit from early immunosuppressive therapy. PMID:23295693

  1. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08.

    PubMed

    Hitz, Felicitas; Zucca, Emanuele; Pabst, Thomas; Fischer, Natalie; Cairoli, Anne; Samaras, Panagiotis; Caspar, Clemens B; Mach, Nicolas; Krasniqi, Fatime; Schmidt, Adrian; Rothermundt, Christian; Enoiu, Milica; Eckhardt, Katrin; Berardi Vilei, Simona; Rondeau, Stephanie; Mey, Ulrich

    2016-07-01

    An increasing number of older patients are suffering from aggressive lymphoma. Effective and more tolerable treatment regimens are urgently needed for this growing patient population. Patients with aggressive lymphoma not eligible for anthracycline-based first-line therapy or intensive salvage regimens were treated with the rituximab-bendamustine-lenalidomide (R-BL) regimen (rituximab 375 mg/m(2)  day 1, bendamustine 70 mg/m(2)  d 1, 2, lenalidomide 10 mg d 1-21) for six cycles every 4 weeks. Forty-one patients with a median age of 75 (range 40-94) years were enrolled: 33 patients had substantial co-morbidities. 13 patients were not eligible for anthracycline-based first-line chemotherapy, 28 patients had relapsed/refractory disease. The primary endpoint, overall response, was achieved by 25 (61%) patients (95% confidence interval 45-76%). Grade ≥ 3 toxicity comprised haematological (59%), skin (15%), constitutional (15%) and neurological (12%) events. 9 patients died during trial treatment: 5 from lymphoma progression, 2 from toxicity, 2 with sudden death. After a median follow-up of 25·9 (interquartile range 20·4-31·6) months, 13 patients were still alive. Median overall survival was 14·5 months. In conclusion, R-BL can be considered a treatment option for elderly patients with treatment naïve or relapsed/refractory aggressive lymphoma not eligible for standard aggressive regimens. PMID:27018242

  2. Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

    PubMed Central

    Stark, D.; Barratt, J. L. N.; van Hal, S.; Marriott, D.; Harkness, J.; Ellis, J. T.

    2009-01-01

    Summary: Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites. PMID:19822892

  3. Sternoclavicular Osteomyelitis in an Immunosuppressed Patient: A Case Report and Review of the Literature

    PubMed Central

    Khan, Kamran; Wozniak, Susan E.; Mehrabi, Erfan; Giannone, Anna Lucia; Dave, Mitul

    2015-01-01

    Patient: Male, 62 Final Diagnosis: Sternoclavicular osteomyelitis Symptoms: — Medication: — Clinical Procedure: Debridement Specialty: Infectious Diseases Objective: Rare disease Background: Sternoclavicular osteomyelitis is a rare disease, with less than 250 cases identified in the past 50 years. We present a rare case of sternoclavicular osteomyelitis in an immunosuppressed patient that developed from a conservatively treated dislocation. Case Report: A 62-year-old white man with a history of metastatic renal cell carcinoma presented to the emergency department (ED) with a dislocated left sternoclavicular joint. He was managed conservatively and subsequently discharged. However, over subsequent days he began to experience pain, fever, chills, and night sweats. He presented to the ED again and imaging revealed osteomyelitis. In the operating room, the wound was aggressively debrided and a wound vac (vacuum-assisted closure) was placed. He was diagnosed with sternoclavicular osteomyelitis and placed on a 6-week course of intravenous Nafcillin. Conclusions: Chemotherapy patients who sustain joint trauma normally associated with a low risk of infection should be monitored thoroughly, and the option to discontinue immunosuppressive therapy should be considered if signs of infection develop. PMID:26708708

  4. Sternoclavicular Osteomyelitis in an Immunosuppressed Patient: A Case Report and Review of the Literature.

    PubMed

    Khan, Kamran; Wozniak, Susan E; Mehrabi, Erfan; Giannone, Anna Lucia; Dave, Mitul

    2015-01-01

    BACKGROUND Sternoclavicular osteomyelitis is a rare disease, with less than 250 cases identified in the past 50 years. We present a rare case of sternoclavicular osteomyelitis in an immunosuppressed patient that developed from a conservatively treated dislocation. CASE REPORT A 62-year-old white man with a history of metastatic renal cell carcinoma presented to the emergency department (ED) with a dislocated left sternoclavicular joint. He was managed conservatively and subsequently discharged. However, over subsequent days he began to experience pain, fever, chills, and night sweats. He presented to the ED again and imaging revealed osteomyelitis. In the operating room, the wound was aggressively debrided and a wound vac (vacuum-assisted closure) was placed. He was diagnosed with sternoclavicular osteomyelitis and placed on a 6-week course of intravenous Nafcillin. CONCLUSIONS Chemotherapy patients who sustain joint trauma normally associated with a low risk of infection should be monitored thoroughly, and the option to discontinue immunosuppressive therapy should be considered if signs of infection develop. PMID:26708708

  5. Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

    PubMed

    Cardell, Markus; Jung, Florian Johannes; Zhai, Wei; Hillinger, Sven; Welp, Andre; Manz, Bernhard; Weder, Walter; Korom, Stephan

    2008-04-01

    Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients. PMID:18339121

  6. Prevention of infection caused by immunosuppressive drugs in gastroenterology

    PubMed Central

    Orlicka, Katarzyna; Barnes, Eleanor

    2013-01-01

    Immunosuppressive therapy is frequently used to treat gastrointestinal diseases such as inflammatory bowel disease, autoimmune hepatitis, IgG4-related disease (autoimmune pancreatitis and sclerosing cholangitis) and in the post-transplantation setting. These drugs interfere with the immune system. The main safety concern with their use is the risk of infections. Certain infections can be prevented or their impact minimized. Physicians must adopt preventative strategies and should have a high degree of suspicion to recognize infections early and treat appropriately. This article reviews the risk factors for infections, the mechanism of action of immunosuppressive therapy and proposes preventive strategies. PMID:23819020

  7. African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

    PubMed

    Malat, Gregory E; Culkin, Christine; Palya, Aniruddha; Ranganna, Karthik; Kumar, Mysore S Anil

    2009-10-22

    Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors

  8. Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal Sarcomas

    PubMed Central

    Yoon, Sam S.; Chen, Yen-Lin; Kirsch, David G.; Maduekwe, Ugwuji N.; Rosenberg, Andrew E.; Nielsen, G. Petur; Sahani, Dushyant V.; Choy, Edwin; Harmon, David C.; DeLaney, Thomas F.

    2010-01-01

    Background We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection. Methods Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin. Results Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence. Conclusions Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease. PMID:20151216

  9. Immunosuppressive treatment for kidney transplantation.

    PubMed

    Zivčić-Ćosić, S; Trobonjača, Z; Rački, S

    2011-01-01

    Immunosuppressive treatment minimizes unwanted immune reactivity, but it also leads to complications such as metabolic disorders, cardiovascular diseases and malignant tumours. In this paper we summarise the recent developments in action mechanisms of available immunosuppressive drugs and their usage for renal transplantation. These drugs act at various levels of lymphocytic activation and proliferation, and they may have additive or synergic effects when combined. In the majority of patients, the immunosuppressive protocol includes a calcineurin inhibitor (tacrolimus or cyclosporin), an antimetabolite (mycophenolate mofetil or mycophenolic acid) and a corticosteroid. Most patients also receive induction with monoclonal or polyclonal antilymphocytic antibodies. These immunosuppressive drugs allow a one-year survival of renal allografts in over 90% of cases and an incidence of acute rejection episodes below 15%. In most cases, acute cell-mediated rejection can be reversed with pulse doses of methylprednisolone; less often antilymphocytic antibodies must be applied. Acute humoral rejection can be suppressed with high doses of intravenous immunoglobulines or low doses of cytomegalovirus hyperimmune globuline, in combination with plasmapheresis, to obtain a satisfactory reduction of anti-donor antibodies. This treatment also allows renal transplantation for sensitised recipients, or transplantation against a positive cross match or AB0 incompatibility. Less often, immunoadsorption, alemtuzumab, rituximab or splenectomy are applied. New immunosuppressive drugs and protocols are currently under investigation. Immunosuppressive agents and methods targeting the induction of immune tolerance to the donor organ are especially promising. PMID:22286615

  10. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort

    PubMed Central

    Walker, AS; Ford, D; Gilks, CF; Munderi, P; Ssali, F; Reid, A; Katabira, E; Grosskurth, H; Mugyenyi, P; Hakim, J; Darbyshire, JH; Gibb, DM; Babiker, AG

    2010-01-01

    Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Methods Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. Findings 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. Interpretation Our results reinforce WHO guidelines and provide strong motivation for provision

  11. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  12. Are Immunosuppressants Becoming Obsolete?

    PubMed

    Lissner, Donata; Siegmund, Britta

    2016-01-01

    Historically, in the 1950s, the introduction of simple, old-fashioned steroids resulted in a significant drop in mortality and hence offered for the first time a real therapeutic option for patients with inflammatory bowel disease. However, as we are all aware of, steroids are no option for maintenance of remission. This review will provide an overview of the available data on the current role of azathioprine in the therapy of Crohn's disease. Based on several controlled trials, the place of azathioprine for maintenance of remission is indisputable. Data from a pediatric cohort suggested that early introduction of azathioprine is beneficial for the disease course. Two recent studies aimed at reproducing these data in adult populations and failed. Hence indicating that azathioprine should only be introduced for maintenance of remission in a step-up-wise approach. An additional role for azathioprine in combo therapy with TNF antibodies has been indicated by several trials revealing a substantial benefit on response. This is partly attributed to the gain in the therapeutic effect by azathioprine itself and possibly through reduction of anti-drug antibody development. In summary, the current role of azathioprine in the therapy of Crohn's disease is manifold and still has an impact in times of targeted therapy. PMID:27548499

  13. Vaccinations in children on immunosuppressive medications for renal disease.

    PubMed

    Banerjee, Sushmita; Dissanayake, Pathum Vindana; Abeyagunawardena, Asiri Samantha

    2016-09-01

    Renal diseases are often treated with immunosuppressive medications, placing patients at risk of infections, some of which are vaccine-preventable. However, in such patients vaccinations may be delayed or disregarded due to complications of the underlying disease process and challenges in its management. The decision to administer vaccines to immunosuppressed children is a risk-benefit balance as such children may have a qualitatively diminished immunological response or develop diseases caused by the vaccine pathogen. Vaccination may cause a flare-up of disease activity or provocation of graft rejection in renal transplant recipients. Moreover, it cannot be assumed that a given antibody level provides the same protection in immunosupressed children as in healthy ones. We have evaluated the safety and efficacy of licensed vaccines in children on immunosuppressive therapy and in renal transplant recipients. The limited evidence available suggests that vaccines are most effective if given early, ideally before the requirement for immunosuppressive therapy, which may require administration of accelerated vaccine courses. Once treatment with immunosuppressive drugs is started, inactivated vaccines are usually considered to be safe when the disease is quiescent, but supplemental doses may be required. In the majority of cases, live vaccines are to be avoided. All vaccines are generally contraindicated within 3-6 months of a renal transplant. PMID:26450774

  14. Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

    PubMed Central

    Kasirye, Yusuf; Epperla, Narendranath; Manne, Janaki Ram; Bapani, Sowjanya; Garcia-Montilla, Romel J

    2012-01-01

    Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy. PMID:22634540

  15. Influenza and Pneumococcal Vaccination Uptake in Patients with Rheumatoid Arthritis Treated with Immunosuppressive Therapy in the UK: A Retrospective Cohort Study Using Data from the Clinical Practice Research Datalink

    PubMed Central

    Winthrop, Kevin L.; Pye, Stephen R.; Brown, Benjamin; Dixon, William G.

    2016-01-01

    Introduction Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK. The aims of this study were to describe the uptake of influenza and pneumococcal vaccinations in patients with RA in the UK, to compare the characteristics of those vaccinated to those not vaccinated and to compare vaccination rates across regions of the UK. Methods A retrospective cohort study of adults diagnosed with incident RA and treated with non-biologic immunosuppressive therapy, using data from a large primary care database. For the influenza vaccination, patients were considered unvaccinated on 1st September each year and upon vaccination their status changed to vaccinated. For pneumococcal vaccination, patients were considered vaccinated after their first vaccination until the end of follow-up. Patients were stratified by age 65 at the start of follow-up, given differences in vaccination guidelines for the general population. Results Overall (N = 15,724), 80% patients received at least one influenza vaccination, and 50% patients received a pneumococcal vaccination, during follow-up (mean 5.3 years). Of those aged below 65 years (N = 9,969), 73% patients had received at least one influenza vaccination, and 43% patients received at least one pneumococcal vaccination. Of those aged over 65 years (N = 5,755), 91% patients received at least one influenza vaccination, and 61% patients had received at least one pneumococcal vaccination. Those vaccinated were older, had more comorbidity and visited the GP more often. Regional differences in vaccination rates were seen with the highest rates in Northern Ireland, and the lowest rates in London. Conclusions One in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over five years of follow-up. There remains significant scope to improve

  16. Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).

    PubMed

    Joly, Véronique; Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-02-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥ 200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥ 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

  17. Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)

    PubMed Central

    Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-01-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

  18. Effect of Surgical Periodontal Therapy on Serum C-reactive Protein Levels Using ELISA in Both Chronic and Aggressive Periodontitis Patient

    PubMed Central

    Gupta, Bharat; Patil, Neha; Yadav, Manoj; Tripathi, Shashank; Sinha, Saurabh; Sharma, Saurabh; Gupta, Saurabh

    2015-01-01

    Background Periodontitis can be defined as a local inflammatory process which mediates destruction of periodontal tissues & is triggered by bacterial insult. In periodontal infections, the levels of C reactive proteins are elevated as compared to the levels in a periodontally healthy individual. The study was done to determine the relative levels of serum CRP in aggressive, chronic and periodontally healthy subjects and to evaluate the effect of surgical periodontal therapy on serum C-reactive protein levels. Materials and Methods Serum samples were collected from 150 participants (50 healthy control patients (non-periodontitis), 50 patients with chronic periodontitis and aggressive periodontitis. Serum C- reactive protein levels were assessed by means of immunoturbidimetric assay at baseline for subjects in all the 3 groups and 3 months after completion of surgical therapy. Results The mean baseline C-reactive protein (CRP) concentrations in the Groups I, II and III were 1.65±0.57 mg/L, 3.03±2.14 mg/L and 3.09±2.27 mg/L respectively. After treatment, the mean C-reactive protein (CRP) levels in Groups II and III reduced from 3.03±1.67 mg/L to 1.46±1.67 mg/L and from 3.09±1.21 to 1.43±1.21 mg/L respectively. Similar results were found for probing depth and all indexes in Group II and III after treatment. Also, the mean attachment loss in Groups II and III reduced, so the results were highly significant. Conclusion Successful periodontal treatment results in significant decrease in serum C-reactive protein (CRP) levels in otherwise healthy subjects. PMID:26557605

  19. Disseminated mucormycosis in a paediatric patient: Lichthemia corymbifera successfully treated with combination antifungal therapy

    PubMed Central

    Campbell, Anita; Cooper, Celia; Davis, Stephen

    2014-01-01

    Mucormycosis is a severe fungal infection that largely affects immunocompromised individuals. It carries a high morbidity and mortality rate and is characterised by extensive angioinvasion and necrosis of host tissue. This case report details success in treating disseminated mucormycosis in a paediatric patient with an underlying haematological malignancy. Treatment included institution of combination antifungal therapy with liposomal amphotericin B and caspofungin, aggressive surgical debridement of infected tissue and reversal of underlying immunosuppression. PMID:25379392

  20. Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials

    PubMed Central

    Subbiah, Ishwaria M.; Falchook, Gerald S.; Kaseb, Ahmed O.; Hess, Kenneth R.; Tsimberidou, Apostolia M.; Fu, Siqing; Subbiah, Vivek; Hong, David S.; Naing, Aung; Sarina, A. Piha-Paul; Akmal, Owais; Janku, Filip; Kurzrock, Razelle

    2015-01-01

    PURPOSE Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapeutic options. Given the rapid advanced in drug development and emergence of novel agents, we analyzed the characteristics and outcomes of HCC patients treated on early phase trials with an emphasis on targeted therapies. METHODS We reviewed the records of consecutive HCC patients evaluated in the Phase I Clinical Trials Program at MD Anderson from March 2004. RESULTS Thirty-nine patients were not treated due to poor performance status (n = 22, 56%) and decision to pursue alternate therapies (n = 10, 27%). Of 61 treated patients (median age, 60 years; median prior therapies, 3), eight patients (13%) attained stable disease lasting ≥6 months; four (7%) had a partial response, mainly with anti-angiogenic or multikinase inhibitors. Median Phase I progression-free survival (PFS) was 2.6 months versus 4.4 months (p 0.019) and 4.1 months (p 0.27) for their first-, and second-line FDA-approved therapy. Molecular analysis showed frequent PTEN loss (10/19 patients, 53%) and P53 mutation (4/4 patients tested). On multivariate analysis, independent factors predicting shorter survival were white ethnicity/race (p 0.031), cirrhosis (p 0.016), and serum sodium (p 0.0013). CONCLUSIONS In our heavily-pretreated HCC patients, the phase I PFS was comparable to that of 2nd-line therapy, highlighting a potential role for clinical trials after progression on first-line therapy. The response rate (SD>6 months/PR) of 20% was observed with early signals of activity in regimens combining inhibitors of angiogenesis, multiple kinases and mTOR with preliminary molecular analysis revealing prevalence of PTEN loss. PMID:26164085

  1. Strongyloidiasis in immunosuppressed hosts. Presentation as massive lower gastrointestinal bleeding.

    PubMed

    Powell, R W; Moss, J P; Nagar, D; Melo, J C; Boram, L H; Anderson, W H; Cheng, S H

    1980-08-01

    Two cases of massive lower gastrointestinal hemorrhage in immunosuppressed patients were due to complicated infestation with Strongyloides stercoralis. The very high mortality of disseminated strongyloidiasis may in part be attributed to delays in diagnosis and treatment resulting from the complex life cycle of this nematode. Successful therapy in the cases presented consisted of reduction of corticosteroid dosage, use of thiabendazole in excess of that recommended for uncomplicated infestation, parenterally administered nutrition, multiple transfusion of blood products, and vigorous supportive management. Emphasis is given to proper categorization of patients and measures designed to prevent, detect, and treat hyperinfection in patients in whom immunosuppression is anticipated. PMID:6967302

  2. IL12 and IL27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors1

    PubMed Central

    Zhu, Shiguo; Lee, Dean Anthony; Li, Shulin

    2010-01-01

    Eradication of residual malignancies and metastatic tumors via a systemic approach is the key for successfully treating cancer and increasing the cancer patient survival. Systemic administration of IL12 protein in an acute large dose is effective but toxic. Systemic administration of IL12 gene by persistently expressing a low level of IL12 protein may reduce the systemic toxicity, but only eradicates IL12 sensitive tumors. Here, we discovered that sequential administration of IL12 and IL27 encoding DNA, referred to as sequential IL12-IL27 gene therapy, not only eradicated IL12 sensitive tumors from 100% of mice but also eradicated the highly malignant 4T1 tumors from 33% of treated mice in multiple independent experiments. This IL12-IL27 sequential gene therapy is not only superior to IL12-IL12 sequential gene therapy for eliminating tumors, but also for inducing CTL activity, increasing T cell infiltration into tumors, and yielding a large number of tumor-specific IFNγ positive CD8 T cells. Notably, depletion of either T- or NK-cells during the IL27 treatment phase reverses tumor eradication, suggesting an NK-cell requirement for this sequential gene therapy-mediated tumor eradication. Both reversal of the administration sequence and co-administration of IL12 and IL27 impaired the tumor eradication in 4T1 tumor bearing mice. This IL12-IL27 sequential gene therapy, via sequential administration of IL12 and IL27 encoding plasmid DNA into tumor-bearing mice through intramuscular electroporation, provides a simple but effective approach for eliminating inaccessible residual tumors. PMID:20139275

  3. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma.

    PubMed

    Zoellner, A-K; Fritsch, S; Prevalsek, D; Engel, N; Hubmann, M; Reibke, R; Rieger, C T; Hellmuth, J C; Haas, M; Mumm, F; Herold, T; Ledderose, G; Hiddemann, W; Dreyling, M; Hausmann, A; Tischer, J

    2015-05-01

    Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory. PMID:25642765

  4. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  5. Prevention of Hepatitis B reactivation in the setting of immunosuppression

    PubMed Central

    Pattullo, Venessa

    2016-01-01

    Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential. PMID:27291888

  6. Bacillary angiomatosis in an immunosuppressed dog.

    PubMed

    Yager, Julie A; Best, Susan J; Maggi, Ricardo G; Varanat, Mrudula; Znajda, Nadine; Breitschwerdt, Edward B

    2010-08-01

    A dog being treated with immunosuppressive doses of prednisone and azathioprine for pancytopenia of unknown origin, developed, over a 2-week period, multiple erythematous nodular lesions in the skin including footpads. Skin samples revealed lesions identical to those of human bacillary angiomatosis (BA). The nodules were composed of multifocal proliferations of capillaries, each lined by protuberant endothelial cells. The capillary clusters were separated by an oedematous connective tissue, lightly infiltrated with degenerate inflammatory cells, including neutrophils and macrophages. Tissue sections stained with Warthin-Starry silver stain revealed large numbers of positively stained bacilli in the stromal tissue, most heavily concentrated around the proliferating capillaries. Lesions of vascular degeneration and inflammation were evident. Bartonella vinsonii subsp. berkhoffii genotype 1 was independently amplified and sequenced from the blood and the skin tissue. The pathognomonic nature of the histological lesions, demonstration of compatible silver-stained bacilli in the tissue, and identification of B. vinsonii subsp. berkhoffii in the blood and tissue indicates that this is most likely the aetiologic agent responsible for the lesions. Antibiotic therapy was successful in resolving the nodules. It would appear that B. vinsonii subsp berkhoffii, like Bartonella henselae and Bartonella quintana, has the rare ability to induce angioproliferative lesions, most likely in association with immunosuppression. The demonstration of lesions identical to those of human BA in this dog is further evidence that the full range of clinical manifestations of human Bartonella infection occurs also in canines. PMID:20374571

  7. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    SciTech Connect

    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.

  8. Long-term genotoxic effects of immunosuppressive drugs on lymphocytes of kidney transplant recipients.

    PubMed

    Lizotti Cilião, Heloísa; Batista de Oliveira Camargo-Godoy, Rossana; Mazzaron Barcelos, Gustavo Rafael; Zanuto, Amanda; Daher Alvares Delfino, Vinicius; de Syllos Cólus, Ilce Mara

    2016-08-01

    Immunosuppressive therapy can prevent rejection after organ transplantation. However, increased cancer risk is a serious complication among patients undergoing such therapy. We have evaluated whether prolonged use of immunosuppressive drugs is genotoxic. DNA instability was assessed, using the comet and micronucleus assays, in blood lymphocytes of 76 kidney transplant patients. DNA damage detected by the comet assay increased with time after transplantation. The estimated glomerular filtration rate of the patients did not influence the incidence of DNA damage. No association between micronucleated mononucleated cells and time elapsed after transplantation was observed. Our results suggest that prolonged use of immunosuppressive drugs in kidney transplant patients can induce genetic instability. PMID:27476335

  9. Association of Human Leukocyte Antigen DRB1*15 and DRB1*15:01 Polymorphisms with Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta-Analysis.

    PubMed

    Liu, Shan; Li, Qing; Zhang, Ying; Li, Qiushuang; Ye, Baodong; Wu, Dijiong; Wu, Li; Lu, Hanti; Ji, Conghua

    2016-01-01

    This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched. All relevant publications were searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95% confidence intervals (CI) for the comparison between case-control or cohort studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33-3.77), P < 0.01 and 2.50(1.73-3.62), P < 0.01, respectively; and the overall pooled RR was 1.72 (1.30-2.29), P < 0.01 and 1.59 (1.29-1.96), P < 0.01, respectively. Statistical evidence showed no publication bias (P > 0.05). Sensitivity analyses revealed that the results were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians. IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients with AA than in HLA-DRB1*15- and HLA-DRB1*15:01- Asian patients with AA. Future studies with adequate methodological quality on gene-gene and gene-environment interactions and gene treatment may yield valid results. PMID:27611583

  10. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients.

    PubMed

    OʼLeary, Jacqueline G; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

  11. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

    PubMed Central

    O'Leary, Jacqueline G.; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

  12. Hematologic toxicity of immunosuppressive treatment.

    PubMed

    Danesi, R; Del Tacca, M

    2004-04-01

    The administration of immunosuppressive agents may be associated with the occurrence of hematologic toxicity, such as anemia, due to bone marrow suppression or hemolysis, leukopenia, and thrombocytopenia. The administration of azathioprine and mycophenolate mofetil is more frequently associated with bone marrow suppression, while hemolytic-uremic syndrome may occur after administration of cyclosporine, tacrolimus, or muromonab (OKT3) and may be associated with the loss of the allograft. Moreover, microangiopathic hemolytic anemia and thrombocytopenia are rare, but potentially severe, complications of immunosuppressive treatment with tacrolimus and cyclosporine; they are characterized by intravascular hemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. Viral infections (cytomegalovirus), administration of antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme and angiotensin II receptor antagonists, antibacterial agents (sulfamethoxazole and trimethoprim), and allopurinol may aggravate bone marrow suppression, particularly when administered with agents that interfere with purine biosynthesis, including azathioprine and mycophenolate mofetil. PMID:15110637

  13. Reduction of delayed renal allograft function using sequential immunosuppression.

    PubMed

    Müller, T; Ruffingshofer, D; Bidmon, B; Arbeiter, K; Balzar, E; Aufricht, C

    2001-08-01

    Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous studies showing that outcome in small children undergoing renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy. PMID:11519888

  14. Sterile post-traumatic immunosuppression.

    PubMed

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-04-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

  15. Sterile post-traumatic immunosuppression

    PubMed Central

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-01-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

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

    PubMed

    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. PMID:25066320

  17. Immunosuppressants

    MedlinePlus

    ... antirejection medicine used at the time of transplant Maintenance drugs: Antirejection medications used for the long term. ... induction drug and the monthly payments are like maintenance drugs. If the down payment is good enough ...

  18. [Filamentous fungal infections in immunosuppressed patients: prophylaxis and treatment].

    PubMed

    Ruiz-Camps, Isabel; Peghin, Maddalena

    2015-09-01

    Although the incidence of invasive aspergillosis has decreased in haematologic patients and solid organ transplant recipients due to the use of prophylaxis; aspergillosis has emerged in other populations undergoing immunosuppressive drugs where prophylaxis is not well defined presenting different clinical patterns. Voriconazole is the gold standard in the treatment of aspergillosis and probably combined therapy, with voriconazole plus anidulafungin, could have a role in the initial management of the infection. PMID:26365733

  19. Aggression in borderline personality disorder.

    PubMed

    Látalová, K; Prasko, J

    2010-09-01

    This review examined aggressive behavior in Borderline Personality Disorder (BPD) and its management in adults. Aggression against self or against others is a core component of BPD. Impulsiveness is a clinical hallmark (as well as a DSM-IV-TR diagnostic criterion) of BPD, and aggressive acts by BPD patients are largely of the impulsive type. BPD has high comorbidity rates with substance use disorders, Bipolar Disorder, and Antisocial Personality Disorder; these conditions further elevate the risk for violence. Treatment of BDP includes psychodynamic, cognitive behavioral, schema therapy, dialectic behavioral, group and pharmacological interventions. Recent studies indicate that many medications, particularly atypical antipsychotics and anticonvulsants, may reduce impulsivity, affective lability as well as irritability and aggressive behavior. But there is still a lack of large, double blind, placebo controlled studies in this area. PMID:20390357

  20. Overcoming the force and power of immunity: a history of immunosuppression in kidney transplantation.

    PubMed

    Patel, Paul S

    2006-01-01

    Immunosuppression for organ transplantation is a modern concept. The earliest reports of organ replacement have their roots in mythology and human fantasy. The primacy of overcoming the immunologic barrier for successful transplantation of organs has been influenced by geopolitical conflict, unorthodox ideas, application of knowledge across medical disciplines, and serendipity. The earliest form of chemical immunosuppression had its origin in chemical gas in warfare. Further developments in immunology, cancer therapy and biochemistry helped shape the intellectual basis for the introduction of chemical immunosuppression. PMID:16874728

  1. Immunosuppressive Treatment for Retinal Degeneration in Juvenile Neuronal Ceroid Lipofuscinosis (Juvenile Batten Disease).

    PubMed

    Drack, Arlene V; Mullins, Robert F; Pfeifer, Wanda L; Augustine, Erika F; Stasheff, Steven F; Hong, Sandy D

    2015-01-01

    Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) presents with progressive vision loss at 4-7 years of age. Blindness results within 2 years, followed by inexorable neurologic decline and death. There is no treatment or cure. Neuroinflammation is postulated to play a role in the neurodegeneration. The JNCL mouse model demonstrated decreased neuroinflammation and improved motor skills with immunosuppression. Based on this work, a short-term human clinical trial of mycophenolate mofetil has begun, however longer term effects, and whether immunosuppression modulates vision loss, have not been studied. We report a JNCL patient treated with immunosuppressive therapy in whom visual function was comprehensively characterized over 2 years. PMID:24547931

  2. Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

    PubMed Central

    Wang, Jennifer; Bartelt, Luther; Yu, Deborah; Joshi, Anjali; Weinbaum, Bradley; Pierson, Tiffany; Patrizio, Michael; Warren, Cirle A.; Hughes, Molly A.; Donowitz, Gerald

    2015-01-01

    Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC) in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy. PMID:25722900

  3. Eruptive disseminated porokeratosis associated with corticosteroid-induced immunosuppression.

    PubMed

    Bednarek, R; Ezra, N; Toubin, Y; Linos, K; Mousdicas, N

    2015-10-01

    Eruptive disseminated porokeratosis (EDP) is a disease that presents clinically with sudden onset of erythematous papules and plaques, with a ridge-like border histologically represented by a cornoid lamella. We report a case of EDP occurring in a 39-year-old woman 3 days after completion of a 2-week course of oral corticosteroid therapy for an acute asthma exacerbation. The patient was treated with emollients and sun protection. Unlike the more chronic disseminated superficial (actinic) porokeratosis, EDP secondary to immunosuppression from corticosteroid therapy has very rarely been reported in the dermatological literature. PMID:25800103

  4. Immunosuppressant-associated neurotoxicity responding to olanzapine.

    PubMed

    Bourgeois, James A; Hategan, Ana

    2014-01-01

    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. PMID:25114826

  5. Autologous hematopoietic stem cell transplantation (AHSCT) for aggressive multiple sclerosis - whom, when and how.

    PubMed

    Szczechowski, Lech; Śmiłowski, Marek; Helbig, Grzegorz; Krawczyk-Kuliś, Małgorzata; Kyrcz-Krzemień, Sławomira

    2016-10-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that leads to an inflammatory process resulting in demyelination and axonal degeneration. The most common form of MS is the relapsing-remitting MS (RRMS) characterized by the presence of numerous relapses. After few years of disease course, 90% of those patients eventually develop a secondary progressive form. About 10% of patients may suffer from a slowly progressive MS form - the primary progressive. The current treatment of RRMS includes immunomodulatory and immunosuppressive agents, which are effective, but usually in earlier and more benign forms. The immunomodulatory treatment has limited efficacy in aggressive forms of RRMS, and relapses occur despite treatment continuation. AHSCT should be considered as a therapeutic approach for patients with aggressive relapsing-remitting and aggressive progressive MS who failed conventional therapy. The mechanism of action of AHSCT for MS results from resetting the aberrant patient's immune system and eliminating the autoreactive T-lymphocytes. AHSCT can serve as an effective and safe procedure only when strict neurological eligibility criteria are adhered. The procedure should be performed in highly specialized hematological centers. The aim of our paper is to summarize the current eligibility criteria for AHSCT in MS patients as well as to present data on efficacy and safety of this approach. PMID:26577419

  6. Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments.

    PubMed

    Giessing, Markus; Fuller, Tom Florian; Tuellmann, Max; Slowinski, Torsten; Budde, Klemens; Liefeldt, Lutz

    2007-06-01

    Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists' knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2-receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX

  7. Adlerian Therapy with Aggressive Children.

    ERIC Educational Resources Information Center

    Kizer, Betty

    Alfred Adler devised a theory that was holistic, social, teleological, and phenomenological. Adler believed that the basis of problems with children originated in the child's inability to cooperate with society, feelings of inferiority, and a lack of a goal in life. Adler felt the child's life should be examined through the child's eyes.…

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

    PubMed Central

    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

  9. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  10. CONCEPT ANALYSIS: AGGRESSION

    PubMed Central

    Liu, Jianghong

    2006-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  11. Concept analysis: aggression.

    PubMed

    Liu, Jianghong

    2004-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

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

    PubMed Central

    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 < 0.001), a higher rate of emergency 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

  13. Immunosuppressive exosomes: a new approach for treating arthritis.

    PubMed

    Yang, Chenjie; Robbins, Paul D

    2012-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease and one of the leading causes of disability in the USA. Although certain biological therapies, including protein and antibodies targeting inflammatory factors such as the tumor necrosis factor, are effective in reducing symptoms of RA, these treatments do not reverse disease. Also, although novel gene therapy approaches have shown promise in preclinical and clinical studies to treat RA, it is still unclear whether gene therapy can be readily and safely applied to treat the large number of RA patients. Recently, nanosized, endocytic-derived membrane vesicles "exosomes" were demonstrated to function in cell-to-cell communication and to possess potent immunoregulatory properties. In particular, immunosuppressive DC-derived exosomes and blood plasma- or serum-derived exosomes have shown potent therapeutic effects in animal models of inflammatory and autoimmune disease including RA. This paper discusses the current knowledge on the production, efficacy, mechanism of action, and potential therapeutic use of immunosuppressive exosomes for arthritis therapy. PMID:22548070

  14. Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

    PubMed

    Lee, Kian-Guan; Teo, Su-Hooi; Lim, Cynthia; Loh, Alwin; Chidambaram, Viswanath; Choo, Jason

    2016-09-01

    Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
. PMID:27443566

  15. Epigenetic regulation of immune cell functions during post-septic immunosuppression

    PubMed Central

    Cavassani, Karen A; Dou, Yali; Kunkel, Steven L

    2011-01-01

    Studies in humans and animal models indicate that profound immunosuppression is one of the chronic consequences of severe sepsis. This immune dysfunction encompasses deficiencies in activation of cells in both the myeloid and lymphoid cell lineages. As a result, survivors of severe sepsis are at risk of succumbing to infections perpetrated by opportunistic pathogens that are normally controlled by a fully functioning immune system. Recent studies have indicated that epigenetic mechanisms may be one driving force behind this immunosuppression, through suppression of proinflammatory gene production and subsequent immune cell activation, proliferation and effector function. A better understanding of epigenetics and post-septic immunosuppression can improve our diagnostic tools and may be an important potential source of novel molecular targets for new therapies. This review will discuss important pathways of immune cell activation affected by severe sepsis, and highlight pathways of epigenetic regulation that may be involved in post-septic immunosuppression. PMID:21048427

  16. Immunosuppression and Chagas Disease: A Management Challenge

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    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 formally

  17. Maintenance immunosuppression regimens: conversion, minimization, withdrawal, and avoidance.

    PubMed

    Yang, Harold

    2006-04-01

    A wide choice of drug combinations is available to clinicians for immunosuppression regimens for their kidney transplant patients. Although many protocols have minimized early graft loss, the optimal long-term regimen is unknown. Recent studies clearly showed that cardiovascular death is now the leading cause of graft loss. Strategies must be developed that address this risk while keeping immunologic events low. Transplant physicians have focused on exploring regimens that minimize or avoid the use of corticosteroids. Studies also have started to explore protocols that minimize calcineurin inhibitor therapy. PMID:16567240

  18. [Polyarteritis nodosa with renal agenesis and immunosuppressive treatment].

    PubMed

    Alcocer, J; Fraga, A; Gudiño, J; Lavalle, C

    1976-01-01

    A case of a 44 years old man with the unique combination of polyarteritis nodosa (PAN) and the congenital absence of a kidney is presented. The clinical picture consisted of fever, general symptoms, hypertermia, peripheric neuropathy, subcutaneous nodules and renal damage. Laboratory findings included increased WBC, telescoped urinary sediment, renal insufficiency, positive rheumatoid factor, policlonal gammopathy and positive Australia antigen. A review of the pertinent literature and the etiopathogenic role of Australia antigen in PAN is discussed. Efficacy of immunosuppressive therapy was evident in this case. PMID:13359

  19. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    PubMed

    Mika, Adriana; Stepnowski, Piotr

    2016-08-01

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. PMID:26874932

  20. A COLLAGENOUS COLITIS-LIKE CONDITION IN IMMUNOSUPPRESSED INFANT BABOONS

    PubMed Central

    Dons, Eefje M.; Echeverri, Gabriel J.; Rigatti, Lora H.; Klein, Edwin; Montoya, Claudia; Wolf, Roman F.; Ijzermans, Jan N.M.; Cooper, David K.C.; Wagner, Robert

    2011-01-01

    Background Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. Case Reports We report four infant baboons (age 7–12 months) that had received a transplant at three months of age and subsequent immunosuppressive therapy for periods of 4–10 months. All presented identical symptoms within a period of four weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). Conclusions Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that (i) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; (ii) it was associated with the immunocompromised state of the baboons, as two non-immunosuppressed age-matched baboons in close proximity did not develop the condition, and (iii) it may have had an infectious origin as all four cases developed within a four week period of time. PMID:22294413

  1. What Is Aggressive Violence?

    ERIC Educational Resources Information Center

    Singer, Dorothy G.; Luca, Wendy

    1985-01-01

    Responses to a questionnaire dealing with what constitutes aggressive violence on television indicate that health care providers tend to rate items describing acts on television as more aggressive than television writers, producers, and executives do. (MBR)

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

    PubMed

    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. PMID:27021338

  3. Unusual case of B cell lymphoma after immunosuppressive treatment for psoriasis.

    PubMed

    Nosotti, Lorenzo; Baiocchini, Andrea; Bonifati, Claudio; Visco-Comandini, Ubaldo; Mirisola, Concetta; Del Nonno, Franca

    2015-04-18

    Lymphomas may be induced by the systemic immunosuppressive therapies used to treat psoriasis, such as ciclosporin, methotrexate and tumour necrosis factor (TNF)-α blockers. The biologic agents currently used in psoriasis include alefacept, efalizumab, and the TNF-α antagonists etanercept, infliximab, and adalimumab. Infections and cancer are the main possible consequences of intended or unexpected immunosuppression. We report a 59-year-old man with a history of severe psoriasis vulgaris treated with traditional immunosuppressant drugs followed by anti-TNF-α therapy; the patient was firstly hospitalized for an acute cholestatic toxic hepatitis, which we supposed to be related to adalimumab. The first liver biopsy showed active disease with severe hepatocellular damage caused by heavy lymphocytes infiltrate in portal tracts at in the interface with a not conclusive diagnosis of lymphoproliferative disease. The correct diagnosis of T cell/histiocyte- rich large B cell lymphoma (T/HRBCL) was only reached through a gastric biopsy and a second liver biopsy. T/HRBCL is an uncommon morphologic variant of diffuse large B-cell lymphoma not described until now in psoriatic patients receiving immunosuppressive biologic agents. In psoriatic patients, treated with biologic immunosuppressive agents, the suspect of abdominal lymphoma should always be included as differential diagnosis. Abdominal ultrasound evaluation need therefore to be included in the pre-treatment screening as in the follow-up surveillance. PMID:25914782

  4. In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection.

    PubMed

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Jones, Brody; Iskandar, Joy; Ahmad, Khansa; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-02-01

    Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she

  5. In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection

    PubMed Central

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Jones, Brody; Iskandar, Joy; Ahmad, Khansa; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-01-01

    Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she

  6. Neurobiological Patterns of Aggression.

    ERIC Educational Resources Information Center

    Hunt, Robert D.

    1993-01-01

    Describes chemical model for patterns of aggressive behavior. Addresses cultural, neurobiological, and cognitive factors that affect violent children. Identifies five patterns of aggression (overaroused, impulsive, affective, predatory, and instrumental) and examines these dimensions of aggression for each pattern: baseline, precipitators,…

  7. Primary laryngeal actinomycosis in an immunosuppressed woman: a case report.

    PubMed

    Abed, Tarik; Ahmed, Jay; O'Shea, Niamh; Payne, Simon; Watters, Gavin W

    2013-07-01

    We report a rare case of primary laryngeal actinomycosis, which occurred in a 35-year-old woman with end-stage renal failure secondary to systemic lupus erythematosus with membranous glomerulonephritis. The patient, who had been on long-term immunosuppression therapy, presented with hoarseness. Flexible laryngoscopy detected the presence of a granular glottic mass at the anterior commissure of the larynx. Histology revealed actinomycotic organisms associated with an abscess. The patient was treated with a prolonged course of oral penicillin V and speech therapy, and her dysphonia resolved almost completely. Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of hoarseness in an immunocompromised patient. PMID:23904305

  8. Long Complete Remission Achieved with the Combination Therapy of Cisplatin and Gemcitabine in a Patient with Aggressive Natural Killer Cell Leukemia

    PubMed Central

    Koepke, John

    2015-01-01

    Aggressive natural killer cell leukemia (ANKL) is a rare and often lethal lymphoproliferative disorder. Patients may present with constitutional symptoms, jaundice, skin infiltration, lymphadenopathy, and hepatosplenomegaly. ANKL can progress quickly to multiorgan failure and survival is usually measured in weeks. Although a rapid and accurate diagnosis is critical, unfortunately there is no hallmark diagnostic marker of ANKL. We report a case of a 48-year-old male who was able to obtain a complete remission following cisplatin-based chemotherapy. We describe the details of the chemotherapy regimens used and a literature review of the treatment of ANKL. PMID:25694835

  9. Increasing Parent Satisfaction of Children's Therapy through an Audio-Visual Investigation of Reactions to Children's Aggressive, Assertive or Passive Anger Responses.

    ERIC Educational Resources Information Center

    Anderson, Fay B.

    This document presents a practicum designed to address the problems encountered when a child in nondirective play therapy becomes able to express emotions and parents, unable to accept their child's new expressions of anger, withdraw the child from therapy at a time when he or she is most vulnerable. The development and implementation of a program…

  10. Relational aggression in marriage.

    PubMed

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression. PMID:20698028

  11. National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

    PubMed

    Axelrod, D A; Naik, A S; Schnitzler, M A; Segev, D L; Dharnidharka, V R; Brennan, D C; Bae, S; Chen, J; Massie, A; Lentine, K L

    2016-08-01

    Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics. PMID:26901466

  12. Immunosuppression of the burned patient.

    PubMed

    Robins, E V

    1989-12-01

    The burn patient is highly susceptible to infection due to the loss of the skin as a barrier to microorganisms. Immune defenses are activated in response to the burn injury; however, some of these defenses are altered. Neutrophil chemotaxis is compromised by decreased perfusion caused by hypovolemia and the formation of microthrombi. Chemotaxis and phagocytosis are dependent on complement components that are reduced in a large burn wound. Neutrophil intracellular killing power is reduced as oxygen delivery to the wound is decreased. Humoral immunity is altered with the drop in IgG levels. Cell-mediated immunity is depressed and T cell lymphocyte counts are deceased. Suppressor T cells are generated. Specific sources of infection for the burn patient include the patient's own bacterial flora; hospital personnel; respiratory equipment; and catheters, both urinary and intravascular. The best control for burn wound infection is the closure of the wound by early excision and grafting. When lack of donor sites prohibits this surgical therapy, control centers on the environment and wound care techniques. The selection of wound topical antibiotics on the basis of visual inspection and surface culturing assists in the prevention of burn wound sepsis. When wound sepsis does occur, systemic antibiotics are instituted. Although burn wound sepsis is an obvious cause of death for the burn patient, it is not the primary cause. Increasing sophistication in fluid resuscitation and in intensive care therapy has resulted in patients living beyond the initial insult and the following few days. Burn patient mortality is now associated with a syndrome presenting clinically as sepsis but without any identifiable septic source.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2697225

  13. Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by reversing immunosuppression in the ovarian cancer microenvironment.

    PubMed

    Baird, Jason R; Fox, Barbara A; Sanders, Kiah L; Lizotte, Patrick H; Cubillos-Ruiz, Juan R; Scarlett, Uciane K; Rutkowski, Melanie R; Conejo-Garcia, Jose R; Fiering, Steven; Bzik, David J

    2013-07-01

    Reversing tumor-associated immunosuppression seems necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the parasite Toxoplasma gondii (T. gondii), which preferentially invades immunosuppressive CD11c(+) antigen-presenting cells in the ovarian carcinoma microenvironment. Tumor-associated CD11c(+) cells invaded by cps were converted to immunostimulatory phenotypes, which expressed increased levels of the T-cell receptor costimulatory molecules CD80 and CD86. In response to cps treatment of the immunosuppressive ovarian tumor environment, CD11c(+) cells regained the ability to efficiently cross-present antigen and prime CD8(+) T-cell responses. Correspondingly, cps treatment markedly increased tumor antigen-specific responses by CD8(+) T cells. Adoptive transfer experiments showed that these antitumor T-cell responses were effective in suppressing solid tumor development. Indeed, intraperitoneal cps treatment triggered rejection of established ID8-VegfA tumors, an aggressive xenograft model of ovarian carcinoma, also conferring a survival benefit in a related aggressive model (ID8-Defb29/Vegf-A). The therapeutic benefit of cps treatment relied on expression of IL-12, but it was unexpectedly independent of MyD88 signaling as well as immune experience with T. gondii. Taken together, our results establish that cps preferentially invades tumor-associated antigen-presenting cells and restores their ability to trigger potent antitumor CD8(+) T-cell responses. Immunochemotherapeutic applications of cps might be broadly useful to reawaken natural immunity in the highly immunosuppressive microenvironment of most solid tumors. PMID:23704211

  14. Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by reversing immunosuppression in the ovarian cancer microenvironment

    PubMed Central

    Baird, Jason R.; Fox, Barbara A.; Sanders, Kiah L.; Lizotte, Patrick H.; Cubillos-Ruiz, Juan R.; Scarlett, Uciane K.; Rutkowski, Melanie R.; Conejo-Garcia, Jose R.; Fiering, Steven; Bzik, David J.

    2013-01-01

    Reversing tumor-associated immunosuppression appears necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the parasite Toxoplasma gondii, which preferentially invades immunosuppressive CD11c+ antigen-presenting cells in the ovarian carcinoma microenvironment. Tumor-associated CD11c+ cells invaded by cps were converted to immunostimulatory phenotypes which expressed increased levels of the T cell receptor co-stimulatory molecules CD80 and CD86. In response to cps treatment of the immunosuppressive ovarian tumor environment, CD11c+ cells regained the ability to efficiently cross-present antigen and prime CD8+ T cell responses. Correspondingly, cps treatment markedly increased tumor antigen-specific responses by CD8+ T cells. Adoptive transfer experiments demonstrated that these antitumor T cell responses were effective in suppressing solid tumor development. Indeed, intraperitoneal cps treatment triggered rejection of established ID8-VegfA tumors, an aggressive xenograft model of ovarian carcinoma, also conferring a survival benefit in a related aggressive model (ID8-Defb29/Vegf-A). The therapeutic benefit of cps treatment relied on expression of IL-12, but it was unexpectedly independent of MyD88 signaling as well as immune experience with T. gondii. Taken together, our results establish that cps preferentially invades tumor-associated antigen-presenting cells and restores their ability to trigger potent antitumor CD8+ T cell responses. Immunochemotherapeutic applications of cps might be broadly useful to reawaken natural immunity in the highly immunosuppressive microenvironment of most solid tumors. PMID:23704211

  15. Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC–MS/MS

    PubMed Central

    Ghareeb, Mwlod; Akhlaghi, Fatemeh

    2015-01-01

    Immunosuppressive drugs used in solid organ transplants typically have narrow therapeutic windows and high intra- and intersubject variability. To ensure satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in any successful posttransplant maintenance therapy. Currently, recommendations for optimum immunosuppressant concentrations are based on blood/plasma measurements. However, they introduce many disadvantages, including poor prediction of allograft survival and toxicity, a weak correlation with drug concentrations at the site of action and the invasive nature of the sample collection. Thus, alternative matrices have been investigated. This paper reviews tandem-mass spectrometry (LC–MS/MS) methods used for the quantification of immunosuppressant drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood and intracellular and intratissue sampling. The advantages, disadvantages and clinical application of such alternative mediums are discussed. Additionally, sample extraction techniques and basic chromatography information regarding these methods are presented in tabulated form. PMID:25966013

  16. [Recognizing and assessing aggressive behaviour in dogs].

    PubMed

    Schalke, E; Hackbarth, H

    2006-03-01

    Within the population the sensitivity to aggressive behaviour in dogs has increased. The authorities are confronted with a problem: if any incident occurs it is their task to decide whether the dogs involved constitute a threat to other people or whether the charge is only the result of a quarrel between neighbours. For this reason, an examination of the dogs with regard to their aggressive behaviour is necessary. Seen from the biological point of view, aggressive behaviour is one of four possibilities a dog can chose from to solve a conflict. The dog's intention in showing aggressive behaviour is to eliminate disturbances and to maintain a distance in space and time. Aggressive behaviour might also be necessary to acquire or defend resources essential to the dog's life. This is to secure its survival and its success in reproduction. One can see from this that aggressive behaviour is a very important and biologically necessary adjustment factor. However, when living together with man aggressive behaviour might become a problem. For the assessment and the therapy of the problem it is necessary to exa-mine the behaviour shown by the dog with regard to its cause. To be able to do this an exact anamnesis, a medical check, and an examination of the dog on the basis of its display in special situations are necessary. For this reason, exclusively veterinarians with a special further education in the field of behaviour should carry out the examination of dogs. PMID:16669189

  17. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    PubMed Central

    2012-01-01

    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 increased risk of pulmonary

  18. Authoritarianism and sexual aggression.

    PubMed

    Walker, W D; Rowe, R C; Quinsey, V L

    1993-11-01

    In Study 1, 198 men completed the Right Wing Authoritarianism, Sex Role Ideology, Hostility Towards Women, Acceptance of Interpersonal Violence, Adversarial Sexual Beliefs, and Rape Myth Acceptance scales, as well as measures of past sexually aggressive behavior and likelihood of future sexual aggression. As predicted, authoritarianism and sex role ideology were as closely related to self-reported past and potential future sexually aggressive behavior as were the specifically sexual and aggression-related predictors. Among 134 men in Study 2, authoritarianism and sex guilt positively correlated with each other and with self-reported past sexual aggression. In both studies, the relationship of authoritarianism and sexual aggression was larger in community than in university samples. PMID:8246111

  19. Maintenance pharmacological immunosuppressive strategies in renal transplantation.

    PubMed Central

    Vella, J. P.; Sayegh, M. H.

    1997-01-01

    Current maintenance immunosuppressive regimens for transplantation are based on three classes of drugs: corticosteroids, immunophilin-binding agents (eg, cyclosporin and tacrolimus), and antimetabolites (eg, azathioprine and mycophenolate). Drugs from the various classes inhibit the immune system at different points and are thus synergistic when used in combination. PMID:9338020

  20. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    PubMed Central

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    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. PMID:27468286

  1. Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation.

    PubMed

    Yaguchi, Tomonori; Kawakami, Yutaka

    2016-08-01

    Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumors. The former is caused by multiple mechanisms via various immunosuppressive molecules and via cells triggered by gene alterations, including activated oncogenes, in cancer cells. The various immunosuppressive mechanisms involve signaling cascades that vary among cancer types, subsets within cancer types and individual cancers. Therefore, personalized immune-interventions are necessary to appropriately target oncogene-induced signaling that modulates anti-cancer immune responses, on the basis of genetic and immunological analysis of each patient. Further understanding of human cancer immunopathology may lead to real improvement of current cancer immunotherapies. PMID:27401477

  2. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens.

    PubMed

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    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. PMID:27468286

  3. Ureteric obstruction due to fungus-ball in a chronically immunosuppressed patient.

    PubMed

    Davis, Niall F; Smyth, Lisa G; Mulcahy, Elizabeth; Scanlon, Tim; Casserly, Liam; Flood, Hugh D

    2013-01-01

    Candida albicans is a fungus that can cause opportunistic urinary tract infections in immunocompromised patients. Disseminated fungaemia secondary to Candida albicans is associated with considerable mortality and therefore merits aggressive treatment. Diagnostic investigations for urosepsis and disseminated fungaemaia secondary to Candida albicans include positive urine and blood cultures. Herein, we describe an extremely unusual case of disseminated fungaemia associated with an obstructive fungus-ball in the distal ureter of an immunosuppressed patient. We also describe a novel application of an established endourological technique for managing this clinical scenario and discuss appropriate perioperative management strategies. PMID:23766839

  4. Practical Approaches to "Top-Down" Therapies for Crohn's Disease.

    PubMed

    Amezaga, Aranzazu Jauregui; Van Assche, Gert

    2016-07-01

    Crohn's disease (CD) is a chronic, progressive, and disabling disease that leads in most cases to the development of bowel damage presenting as a fistula, abscess, or stricture. For years, therapy for Crohn's disease has been based on a "step-up" approach, in which anti-TNF agents are administered after the failure of steroids and immunosuppressants. However, recent studies have suggested that early introduction of anti-TNF agents combined with immunosuppressants can modify the natural history of the disease. Patients who could benefit more of this "top-down" strategy would be those at elevated risk of a complicated or severe inflammatory bowel disease or with factors that can predict an aggressive disease course. Therefore, the management of a patient with CD should be personalized, taking into account the patient's specific characteristics and comorbidities, disease activity, site and behavior of the disease, and predictable factors of poor prognosis. A balance between medication and potential adverse effects should be achieved, trying to avoid under or overtreatment, always discussing the different therapeutic options with the patient. The natural history of ulcerative colitis differs from CD and, to date, there is not much scientific evidence on the use of early combined immunosuppression. PMID:27184044

  5. Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects of tacrolimus, cyclosporine, and prednisone.

    PubMed

    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 < .03, P < .009, and P < .002, respectively). There was no difference in MCAT, whereas MSBTT was longer for tacrolimus and prednisone compared with control subjects (P < .004 and P < .004, respectively). Also, 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. PMID:25131057

  6. Angry and Aggressive Students

    ERIC Educational Resources Information Center

    Larson, Jim

    2008-01-01

    Students who engage in physical aggression in school present a serious challenge to maintaining a safe and supportive learning environment. Unlike other forms of student aggression, fighting is explicit, is violent, and demands attention. A fight between students in a classroom, hallway, or the lunchroom brings every other activity to a halt and…

  7. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  8. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  9. Aggression: Psychopharmacologic Management

    PubMed Central

    Conlon, Patrick; Frommhold, Kristine

    1989-01-01

    Aggression may be part of a variety of psychiatric diagnoses. The appropriate treatment requires that the physician recognize the underlying cause. Pharmacologic agents may form part of the overall treatment of the patient. The number of possible drugs for treating aggression has expanded rapidly, and it is important that the physician be familiar with the various options avilable. PMID:21248947

  10. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  11. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  12. Neuropsychiatry of Aggression

    PubMed Central

    Lane, Scott D.; Kjome, Kimberly L.; Moeller, F. Gerard

    2010-01-01

    Synopsis Aggression is a serious medical problem that can place both the patient and the health care provider at risk. Aggression can result from medical, neurologic and or psychiatric disorders. A comprehensive patient evaluation is needed. Treatment options include pharmacotherapy as well as non-pharmacologic interventions, both need to be individualized to the patient. PMID:21172570

  13. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, T; Prayoonwiwat, W; Numbenjapon, T; Assawametha, N; O'Charoen, R; Swasdikul, D

    2000-12-01

    The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL. PMID:11707834

  14. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)*

    PubMed Central

    Lejeune, A.; Skorupski, K.; Frazier, S.; Vanhaezebrouck, I.; Rebhun, R. B.; Reilly, C. M.; Rodriguez, C. O.

    2016-01-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease-free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months. PMID:23721492

  15. Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

    SciTech Connect

    Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.; Fabian, R.L.; Miller, D.

    1982-05-01

    A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications, possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity.

  16. Induction and escalation therapies in multiple sclerosis.

    PubMed

    Fenu, G; Lorefice, L; Frau, F; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system. Pharmacological therapy of MS includes symptomatic drugs, treatment for relapses (corticosteroid and intravenous immunoglobulin) and disease modifying drugs (DMDs) defined as pharmacological agents that have an impact on relapse rate, disability accumulation and radiological outcomes. Two different therapeutic approaches are widely used in MS: escalation and induction therapy. Escalation therapy consists of an early start with first line DMDs (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are ineffective or partially effective, switching to second line drugs (mitoxantrone, natalizumab, fingolimod). Induction therapy consists of the early use of immunosuppressant drugs followed by long-term maintenance treatment, generally with immunomodulatory agents. While the use of natalizumab and fingolimod as first line drugs is indicated for aggressive forms of MS, the indication for mitoxantrone as an induction treatment arises from randomized studies demonstrating that induction therapy with mitoxantrone followed by DMD maintenance is more effective than monotherapy with beta interferon. However, the safety profile of induction drugs indicates this is not an acceptable therapeutic strategy for all MS patients in all phases of the disease. The upcoming challenge is to identify patients at high risk of disability development from their clinical characteristics, radiological findings or biomarkers. Furthermore, future studies to establish an individual safety profile stratification are needed. PMID:25938688

  17. Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease.

    PubMed

    Ma, Christopher; Walters, Brennan; Fedorak, Richard N

    2013-06-01

    Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy. PMID:23745038

  18. Adherence to immunosuppression: a prospective diary study.

    PubMed

    Gordon, E J; Prohaska, T R; Gallant, M P; Siminoff, L A

    2007-12-01

    Immunosuppression adherence among kidney transplant recipients is essential for graft survival. However, nonadherence is common, jeopardizing graft survival. Besides skipping dosages, little is known about other forms of medication nonadherence and their underlying reasons. This study sought to examine patients' extent of medication adherence over time and reasons for nonadherence. Thirty-nine new kidney transplant recipients were asked to complete a month-long medication-taking diary that included reporting medication nonadherence such as skipped medications, medications taken early or late, taking dosages greater or less than prescribed, and the reason for each occurrence of nonadherence. Of the 20 (51%) patients who completed the diary, 11 (55%) reported at least 1 form of nonadherence. Eleven patients reported taking their immunosuppression at least 1 hour later than the prescribed time, 1 patient reported skipping medication, but no patients reported changing the dosage on their own. Immunosuppression was taken on average 1.5 hours after the prescribed time. Of those patients who took their medications late, there were on average 3.1 occasions of taking it late. The most common reasons for this behavior included health care-related issues, followed by oversleeping, being away from home, work-related barriers, and forgetting. The majority of kidney transplant recipients took medications later than prescribed during 1 month. Future research should determine the clinical impact on graft function of late administration of immunosuppression. Interventions should be designed to better assist kidney recipients with taking medications on time, especially when they are away from home. PMID:18089327

  19. UV-induced immunosuppression in the balance.

    PubMed

    de Gruijl, Frank R

    2008-01-01

    Around 1980, experiments with hairless mice showed us that UV-induced actinic keratoses (AK) and ensuing skin carcinomas did not arise independently: the rate of occurrence in one skin area was increased considerably if AKs had already been induced separately in another distant skin area, i.e. a systemic effect. The ground laying work of Margaret Kripke in the 1970s provided a fitting explanation: UV-induced immunosuppression and tolerance toward the UV-induced tumors. From Kripke's work a new discipline arose: "Photoimmunology." Enormous strides were made in exploring and expanding the effects from UV carcinogenesis to infectious diseases, and in elucidating the mechanisms involved. Stemming from concerns about a depletion of the ozone layer and the general impact of ambient UV radiation, the groups I worked in and closely collaborated with explored the anticipated adverse effects of UV-induced immunosuppression on healthy individuals. An important turning point was brought about in 1992 when the group of Kevin Cooper reported that immunosuppression could be induced by UV exposure in virtually all human subjects tested, suggesting that this is a normal and sound physiological reaction to UV exposure. This reaction could actually protect us from illicit immune responses against our UV-exposed skin, such as observed in idiopathic polymorphic light eruption. This premise has fruitfully rekindled the research on this common "sun allergy," affecting to widely varying degrees about one in five Europeans with indoor professions. PMID:18173695

  20. [The immunosuppressive microenvironment of malignant gliomas].

    PubMed

    Borisov, K E; Sakaeva, D D

    2015-01-01

    The dogma of the central nervous system (CNS) as an immune-privileged site has been substantially revised in recent years. CNS is an immunocompetent organ and actively interacts with the immune system. Microglia plays a leading role in a CNS immune response. However, in malignant gliomas, there is M2-polarization of microglia acquiring immunosuppressive and tumor-supportive properties. It occurs under the influence of tumor cytokines, such as transforming growth factor-β, interleukin-10, and prostaglandin E2. M2-polarized microglia exhibits reduced phagocytic activity, changes in the expression of many cellular determinants, or inverse of their functions, STAT3 activation, and production of immunosuppressive cytokines that suppress the function of cytotoxic CD8+ T cells or CD4+ T-helper cells type I. Myeloid-derived suppressor cells and regulatory T-lymphocytes, which have been recruited from peripheral blood into tumor tissue, also have immunosuppressive properties. The development of new treatment options for malignant gliomas must consider the role of the microenvironment in maintaining tumor vitality and progression. PMID:26841651

  1. Management of immunosuppressant agents following liver transplantation: Less is more

    PubMed Central

    Ascha, Mustafa S; Ascha, Mona L; Hanouneh, Ibrahim A

    2016-01-01

    Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient. PMID:26839639

  2. [Immunosuppressive treatment of rheumatic diseases. Experimental bases of a rational concept of therapeutic approach (author's transl)].

    PubMed

    Lemmel, E M; Botzenhardt, U

    1976-01-01

    For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the

  3. Minimization vs tailoring: Where do we stand with personalized immunosuppression during renal transplantation in 2015?

    PubMed Central

    Zsom, Lajos; Wagner, László; Fülöp, Tibor

    2015-01-01

    The introduction of novel immunosuppressive agents over the last two decades and the improvement of our diagnostic tools for early detection of antibody-mediated injury offer us an opportunity, if not a mandate, to better match the immunosuppression needs of the individual patients with side effects of the therapy. However, immunosuppressive regimens in the majority of programs remain mostly protocol-driven, with relatively little inter-program heterogeneity in certain areas of the world. Emerging data showing different outcomes with a particular immunosuppressive strategy in populations with varying immunological risks underscore a real potential for “personalized medicine” in renal transplantation. Studies demonstrating marked differences in the adverse-effect profiles of individual drugs including the risk for viral infections, malignancy and renal toxicity call for a paradigm shift away from a “one size fits all” approach to an individually tailored immunosuppressive therapy for renal transplant recipients, assisted by both screening for predictors of graft loss and paying close attention to dose or class-related adverse effects. Our paper explores some of the opportunities during the care of these patients. Potential areas of improvements may include: (1) a thorough assessment of immunological and metabolic risk profile of each renal transplant recipient; (2) screening for predictors of graft loss and early signs of antibody-mediated rejection with donor-specific antibodies, protocol biopsies and proteinuria (including close follow up of adverse effects with dose adjustments or conversions as necessary); and (3) increased awareness of the possible link between poor tolerance of a given drug at a given dose and non-adherence with the prescribed regimen. Altogether, these considerations may enable the most effective use of the drugs we already have. PMID:26421259

  4. Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

    PubMed Central

    Bessone, Fernando; Dirchwolf, Melisa

    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. PMID:27004086

  5. Linkages between Aggression and Children's Legitimacy of Aggression Beliefs.

    ERIC Educational Resources Information Center

    Erdley, Cynthia A.; Asher, Steven R.

    To determine whether Slaby and Guerra's (1988) measure of aggression would reliably assess younger children's belief about aggression and whether children's belief about the legitimacy of aggression relates to their self-reports of it and to their levels of aggression as evaluated by peers, 781 fourth and fifth graders were asked to complete an…

  6. Aggressive Attitudes Predict Aggressive Behavior in Middle School Students.

    ERIC Educational Resources Information Center

    McConville, David W.; Cornell, Dewey G.

    2003-01-01

    This prospective study found that self-reported attitudes toward peer aggression among 403 middle school students were both internally consistent and stable over time (7 months). Aggressive attitudes were correlated with four outcome criteria for aggressive behavior: student self-report of peer aggression; peer and teacher nominations of bullying;…

  7. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  8. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

    PubMed Central

    Bamgbola, Oluwatoyin

    2016-01-01

    Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival. PMID:27293540

  9. Holy Basil Leaf Extract Decreases Tumorigenicity and Metastasis of Aggressive Human Pancreatic Cancer Cells in vitro and in vivo: Potential Role in Therapy

    PubMed Central

    Shimizu, Tomohiro; Torres, María P.; Chakraborty, Subhankar; Souchek, Joshua J.; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K.; Hauke, Ralph J; Batra, Surinder K.

    2013-01-01

    There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

  10. Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: potential role in therapy.

    PubMed

    Shimizu, Tomohiro; Torres, María P; Chakraborty, Subhankar; Souchek, Joshua J; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K; Hauke, Ralph J; Batra, Surinder K

    2013-08-19

    There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum ("Holy Basil") has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

  11. Pleurotus nebrodensis polysaccharide (PN-S) enhances the immunity of immunosuppressed mice.

    PubMed

    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. PMID:26481376

  12. Photodynamic therapy for treatment of AIDS-related mucocutaneous Kaposi's sarcoma (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1992-06-01

    Since 1975, Phase I/II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy (PDT) in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, in 1981 two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts to cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of mucocutaneous Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions (endothelial cell tumors); (2) a tumor- specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; (4) the potential for retreatment without increasing side effects; and (5) porphyrin-mediated photoinactivation of enveloped viruses. Herein presented are seven cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular mucocutaneous lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.

  13. Enteric glial cells have specific immunosuppressive properties.

    PubMed

    Kermarrec, Laetitia; Durand, Tony; Neunlist, Michel; Naveilhan, Philippe; Neveu, Isabelle

    2016-06-15

    Enteric glial cells (EGC) have trophic and neuroregulatory functions in the enteric nervous system, but whether they exert a direct effect on immune cells is unknown. Here, we used co-cultures to show that human EGC can inhibit the proliferation of activated T lymphocytes. Interestingly, EGC from Crohn's patients were effective at one EGC for two T cells whereas EGC from control patients required a ratio of 1:1. These data suggest that EGC contribute to local immune homeostasis in the gastrointestinal wall. They also raise the possibility that EGC have particular immunosuppressive properties in inflammatory bowel diseases such as Crohn's disease. PMID:27235353

  14. 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?

    PubMed Central

    Welling, John D; Tarabishy, Ahmad B; Christoforidis, John B

    2012-01-01

    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. PMID:22570539

  15. Response-Adapted Therapy for Aggressive non-Hodgkin's Lymphomas based on early [18F] FDG-PET Scanning: ECOG-ACRIN Cancer Research Group Study (E3404)

    PubMed Central

    Swinnen, Lode J.; Li, Hailun; Quon, Andrew; Gascoyne, Randy; Hong, Fangxin; Ranheim, Erik A.; Habermann, Thomas M.; Kahl, Brad S.; Horning, Sandra J.; Advani, Ranjana H.

    2015-01-01

    A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B-cell lymphoma (DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received 4 cycles of R-ICE, PET-negative patients received 2 more cycles of R-CHOP. A ≥45% 2-year progression-free survival (PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% (90% confidence interval [CI], 19-63%) for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival (OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and –negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R-ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. PMID:25823885

  16. Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome

    PubMed Central

    Werner, Robert; Vollbrecht, Claudia; Hager, Thomas; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Christoph, Daniel Christian

    2016-01-01

    Purpose 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. Experimental Design Sixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair. Results Expression of FOLR1, FPGS, MLH1 and TYMS (each p<0.0001) differed significantly between all four tumor types. FOLR1 and FPGS associated with tumor differentiation (both p<0.0001), spread to regional lymph nodes (FOLR1 p=0.0001 and FPGS p=0.0038), OS and PFS (FOLR1 p<0.0050 for both and FPGS p<0.0004 for OS). Phenotypic sorting revealed the Ft-phenotype to be the most prominent expression profile in carcinoids, whereas SCLC presented nearly univocal with the fT and LCNEC with fT or ft. These results were significant for tumor subtype (p<0.0001). Conclusions The assessed biomarkers and phenotypes allow for risk stratification (OS, PFS), diagnostic classification and enhance the biological understanding of the different subtypes of neuroendocrine tumors revealing potential new therapy options and clarifying known resistance mechanisms. PMID:27064343

  17. Menopause in women with chronic immunosuppressive treatment - how to help those patients.

    PubMed

    Cyganek, Anna; Pietrzak, Bronisława; Wielgoś, Mirosław; Grzechocińska, Barbara

    2016-03-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment. PMID:27095951

  18. Menopause in women with chronic immunosuppressive treatment – how to help those patients

    PubMed Central

    Pietrzak, Bronisława; Wielgoś, Mirosław; Grzechocińska, Barbara

    2016-01-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment. PMID:27095951

  19. The combination of immunosuppressive drugs with 8-methoxypsoralen and ultraviolet a light modulates the myeloid-derived dendritic cell function.

    PubMed

    Failli, A; Legitimo, A; Mazzoni, A; Urbani, L; Scatena, F; Mosca, F; Consolini, R

    2011-01-01

    The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither

  20. Remission and withdrawal of therapy in lupus nephritis.

    PubMed

    Moroni, Gabriella; Raffiotta, Francesca; Ponticelli, Claudio

    2016-08-01

    There is agreement that early diagnosis and aggressive treatment of lupus nephritis exacerbations are of paramount importance to achieve remission and prevent the development of irreversible lesions. There is less agreement about the optimal duration of maintenance treatment. Instead, the prolonged exposure to corticosteroids and/or immunosuppressive drugs can cause invalidating or even life-threatening complications. It is still unclear if these drugs can be safely withdrawn in lupus patients. We were able to completely withdraw therapy in around 1/3 of our patients after a follow-up of 5 years or more; 60 % of them never had to start therapy again. Based on our own experience, discontinuation of therapy should be applied only in selected cases, i.e. patients who received maintenance therapy for at least 5 years and are in complete renal remission for at least 3 years. Antimalarial agents are helpful in maintaining the remission after withdrawal of therapy. However, to achieve these goals, drugs should be tapered off very slowly and under strict surveillance. If all these prerequisites are satisfied, the withdrawal of therapy in patients with lupus nephritis may be considered safe, may improve the patients' quality of life and may reduce the damage accrual. PMID:27146861

  1. Local brain heavy ion irradiation induced Immunosuppression

    NASA Astrophysics Data System (ADS)

    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.

  2. Adolescents’ Aggression to Parents: Longitudinal Links with Parents’ Physical Aggression

    PubMed Central

    Margolin, Gayla; Baucom, Brian R.

    2014-01-01

    Purpose To investigate whether parents’ previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents’ subsequent parent-directed aggression even beyond parents’ concurrent physical aggression (CPA); to investigate whether adolescents’ emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Methods Adolescents (N = 93) and their parents participated in a prospective, longitudinal study. Adolescents and parents reported at waves 1–3 on four types of parents’ PPA (mother-to-adolescent, father-to-adolescent, mother-to-father, father-to-mother). Wave 3 assessments also included adolescents’ emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents’ parent-directed physical aggression, property damage, and verbal aggression, and on parents’ CPA Results Parents’ PPA emerged as a significant indicator of adolescents’ parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0–1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1–1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15–1.6, p < .001) even controlling for adolescents’ sex, externalizing behaviors, and family income. When controlling for parents’ CPA, previous mother-to-adolescent aggression still predicted adolescents’ parent-directed physical aggression (OR: 5.56, 95% CI: 1.82–17.0, p = .003), and father-to-mother aggression predicted adolescents’ parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0–3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated effects. Conclusions Adolescents’ parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents’ physical aggression. Future research should investigate parent-directed aggression as

  3. Immunosuppressive cells in tumor immune escape and metastasis.

    PubMed

    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. PMID:26689709

  4. Anti-arthritic and immunosuppressive activities of substituted triterpenoidal candidates.

    PubMed

    Alanazi, Amer M; Al-Omar, Mohamed A; Abdulla, Mohamed M; Amr, Abd El-Galil E

    2013-07-01

    We herein report the anti-arthritic and immunosuppressive activities of some synthesized substituted terpenoidal structure. Forty-four triterpenoid derivatives 1-21 containing a carboxylic, ester, amide and ketone groups attached to a triterpene moiety were conveniently synthesized and screened for their anti-arthritic and immunosuppressive activities. Synthetic triterpenoidal structures linked to a different function groups seem to be a promising approach in the search for novel leads for potent anti-arthritic and immunosuppressive agents. The detailed synthetic pathways of obtained compounds and anti-arthritic and immunosuppressive activities were reported. PMID:23603083

  5. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    PubMed Central

    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. PMID:26558118

  6. Microbiology of aggressive periodontitis.

    PubMed

    Könönen, Eija; Müller, Hans-Peter

    2014-06-01

    For decades, Aggregatibacter actinomycetemcomitans has been considered the most likely etiologic agent in aggressive periodontitis. Implementation of DNA-based microbiologic methodologies has considerably improved our understanding of the composition of subgingival biofilms, and advanced open-ended molecular techniques even allow for genome mapping of the whole bacterial spectrum in a sample and characterization of both the cultivable and not-yet-cultivable microbiota associated with periodontal health and disease. Currently, A. actinomycetemcomitans is regarded as a minor component of the resident oral microbiota and as an opportunistic pathogen in some individuals. Its specific JP2 clone, however, shows properties of a true exogenous pathogen and has an important role in the development of aggressive periodontitis in certain populations. Still, limited data exist on the impact of other microbes specifically in aggressive periodontitis. Despite a wide heterogeneity of bacteria, especially in subgingival samples collected from patients, bacteria of the red complex in particular, and those of the orange complex, are considered as potential pathogens in generalized aggressive periodontitis. These types of bacterial findings closely resemble those found for chronic periodontitis, representing a mixed polymicrobial infection without a clear association with any specific microorganism. In aggressive periodontitis, the role of novel and not-yet-cultivable bacteria has not yet been elucidated. There are geographic and ethnic differences in the carriage of periodontitis-associated microorganisms, and they need to be taken into account when comparing study reports on periodontal microbiology in different study populations. In the present review, we provide an overview on the colonization of potential periodontal pathogens in childhood and adolescence, and on specific microorganisms that have been suspected for their role in the initiation and progression of aggressive

  7. Cytomegalovirus infection impairs immunosuppressive and antimicrobial effector functions of human multipotent mesenchymal stromal cells.

    PubMed

    Meisel, Roland; Heseler, Kathrin; Nau, Julia; Schmidt, Silvia Kathrin; Leineweber, Margret; Pudelko, Sabine; Wenning, Johannes; Zimmermann, Albert; Hengel, Hartmut; Sinzger, Christian; Degistirici, Özer; Sorg, Rüdiger Volker; Däubener, Walter

    2014-01-01

    Human mesenchymal stromal cells (MSC) possess immunosuppressive and antimicrobial effects that are partly mediated by the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Therefore MSC represent a promising novel cellular immunosuppressant which has the potential to control steroid-refractory acute graft versus host disease (GvHD). In addition, MSC are capable of reducing the risk of infection in patients after haematopoietic stem cell transplantation (HST). Recent data indicate that signals from the microenvironment including those from microbes may modulate MSC effector functions. As Cytomegalovirus (CMV) represents a prominent pathogen in immunocompromised hosts, especially in patients following HST, we investigated the impact of CMV infection on MSC-mediated effects on the immune system. We demonstrate that CMV-infected MSC lose their cytokine-induced immunosuppressive capacity and are no longer able to restrict microbial growth. IDO expression is substantially impaired following CMV infection of MSC and this interaction critically depends on intact virus and the number of MSC as well as the viral load. Since overt CMV infection may undermine the clinical efficacy of MSC in the treatment of GvHD in transplant patients, we recommend that patients scheduled for MSC therapy should undergo thorough evaluation for an active CMV infection and receive CMV-directed antiviral therapy prior to the administration of MSC. PMID:24782599

  8. New puzzles for the use of non-invasive ventilation for immunosuppressed patients.

    PubMed

    Barbas, Carmen Sílvia Valente; Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled "Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial", which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID:26904233

  9. New puzzles for the use of non-invasive ventilation for immunosuppressed patients

    PubMed Central

    Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled “Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial”, which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID:26904233

  10. Plasmaphresis therapy for pulmonary hemorrhage in a pediatric patient with IgA nephropathy

    PubMed Central

    Yim, Dae-Kyoon; Lee, Sang-Taek

    2015-01-01

    IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage. PMID:26576186

  11. [Infections and immunosuppressive agents in rheumatology].

    PubMed

    Kahn, M F; Vitale, C; Grimaldi, A

    The authors review the problem of infection occurring in patients with chronic inflammatory rheumatism, e.g. rheumatoid arthritis, and lupus erythematosus, treated with cytolytic drugs for immunodepressive reasons. From their investigation, it seems that there is a high frequency of bacterial and mycotic and viral infections in these patients, but controlled investigations seem to show quite definitely that the frequency of these infections depends on the disease itself. The risk does not seem to be increased by cytolytic drugs. The only exception is herpes which appears in 10 to 20% of patients treated with immunosuppressive agents, as against 2% in a controll series. The other virus diseases did not have an abnormally high frequency. The conclusions are, of course, only of value for the types of treatment used in rheumatology. PMID:183273

  12. Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

    PubMed

    Rajmani, R S; Singh, Prafull Kumar; Kumar, Sanjay; Kumar, G Ravi; Sahoo, Aditya P; Santra, Lakshman; Saxena, Shikha; Singh, Lakshya Veer; Chaturvedi, Uttara; Saxena, Lovleen; Desai, G S; Gupta, Shishir Kumar; Kumar, Amit; Jadon, N S; Tiwari, Ashok K

    2014-10-01

    Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and gamma-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection. PMID:25345242

  13. Hyperkeratotic variant of porokeratosis in a patient with Hepatitis C virus infection and a concomitant immunosuppressed state.

    PubMed

    Parekh, Vishwas; Kabihting, Filamer D; Junkins-Hopkins, Jacqueline M

    2015-11-01

    Porokeratoses are acquired and hereditary disorders of keratinization that share a distinctive lesion characterized by raised keratotic borders corresponding histologically to an angled column of parakeratotic cells, called a cornoid lamella. Although a precise mechanistic explanation is lacking, ultraviolet radiation and immunosuppressed states are considered causally-associated with most cases of acquired porokeratosis. Hepatitis C virus (HCV) infection has been proposed as a link between the immunosuppressed states and development of acquired porokeratosis. Among the various recognized clinical entities that constitute this group, rare cases of hyperkeratotic variants have been described that may pose a diagnostic challenge. Herein we describe a remarkable case of the hyperkeratotic variant of porokeratosis that occurred in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state. We also provide a review of the relevant literature. PMID:26632932

  14. Intellectual Competence and Aggression.

    ERIC Educational Resources Information Center

    Huesmann, L. Rowell; Yarmel, Patty Warnick

    Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…

  15. Relational Aggression among Students

    ERIC Educational Resources Information Center

    Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.

    2011-01-01

    "Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…

  16. Stability of Aggressive Behavior.

    ERIC Educational Resources Information Center

    Eron, Leonard D.; Huesmann, L. Rowell

    As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

  17. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  18. Anonymity, Deindividuation and Aggression.

    ERIC Educational Resources Information Center

    Baron, Robert S.

    Several writers suggest that reducing one's sense of individuality reduces social restraints. The author suggests that the effect of uniformity of appearance on aggression is unclear when anonymity is held constant. This poses a problem of interpretation given that a distinction must be made between lack of individuality and anonymity. One must…

  19. Prevention of infection in immunosuppressive patients with autoimmune nephrosis by using an immunostimulating bacterial lysate Broncho-vaxom

    PubMed Central

    Zhang, Miao; Luan, Hong; Zhang, Qian; Wang, Le; Lv, Yong-Man; He, Fan; Chen, Yan; Zeng, Hong-Bing; Yao, Ying; Liu, Qin

    2012-01-01

    The utilization of immunosuppressive agents presents patients with autoimmune nephrosis at a high risk of infection. The present trial was to investigate the efficacy and safety of Broncho-Vaxom on preventing infection in immunosuppressive patients with autoimmune nephrosis. Methods: 40 patients with autoimmune nephrosis were randomly divided into two groups. The control group (20 cases) routinely received corticosteroid and (or) immunosuppressive therapy, while the treatment group (20 cases) received a capsule containing 7 mg Broncho-Vaxom daily for the first 10 d of each month for 3 consecutive months on the basis of conventional corticosteroid and (or) immunosuppressive therapy. The condition of infection and blood lymphocyte were assessed. Results: 4 patients in the treatment group and 5 patients in the control group were lost during the follow-up period. 25% of patients in the treatment group and 40% of patients in the control group suffered infection. There was no difference in the incidence of infection between the two groups (p > 0.05), while Broncho-Vaxom treated patients suffered a shorter infection period and of which fewer patients need to receive antibiotics therapy (p < 0.05). After the treatment with Broncho-Vaxom, the total number of blood T lymphocyte, proportion of CD4+ T lymphocyte, CD4+/CD8+ reduced less and the serum IgG rose more obviously (p < 0.05), but the blood lymphocyte, B lymphocyte, CD8+ T lymphocyte, IgA and IgM have no differences between the two groups (p > 0.05). Conclusion: Broncho-Vaxom might be a good choice for preventing the respiratory infection in nephrosis, especially in the patients under the therapy of immunosuppressive agents. PMID:22922768

  20. Parents' Aggressive Influences and Children's Aggressive Problem Solutions with Peers

    ERIC Educational Resources Information Center

    Duman, Sarah; Margolin, Gayla

    2007-01-01

    This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…

  1. Relational Aggression and Physical Aggression among Adolescent Cook Islands Students

    ERIC Educational Resources Information Center

    Page, Angela; Smith, Lisa F.

    2016-01-01

    Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…

  2. The portal immunosuppressive storm: relevance to islet transplantation?

    PubMed

    Shapiro, A M James; Gallant, Heather L; Hao, Er Geng; Lakey, Jonathan R T; McCready, Tara; Rajotte, Ray V; Yatscoff, Randall W; Kneteman, Norman M

    2005-02-01

    Outcomes in clinical islet transplantation improved substantially with the introduction of combined sirolimus and tacrolimus immunosuppression. However, multiple islet preparations are often required to achieve insulin independence, suggesting that islet engraftment may not be optimal when these agents are absorbed via the portal vein. The current study was designed to assess the differential concentrations of immunosuppressive drugs within the portal and systemic circulations of a large animal model, to assess the local concentrations of drugs to which islets are exposed early after implantation. Chronic catheters were placed in the portal vein and carotid artery of 6 mongrel dogs, and immunosuppressants were administered orally. Blood samples were drawn simultaneously from portal and systemic catheters, and drug concentrations were analyzed. Peak immunosuppressant levels as well as area under the curve were dramatically elevated in portal blood relative to systemic levels for all drugs tested. This "portal storm" of immunosuppression may be relevant to intrahepatic islet transplantation. PMID:15665744

  3. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

    White subjects were aggressive toward Black opponents when contest results appeared to reflect elements of reverse discrimination; but they showed less aggressive behavior toward Black opponents when they thought their loss was due to their opponents' superior ability. (RL)

  4. Coping with Agitation and Aggression

    MedlinePlus

    Alzheimer ’s Caregiving Tips Coping with Agitation and Aggression People with Alzheimer’s disease may become agitated or aggressive as the disease gets worse. Agitation means that a person is restless or worried. ...

  5. The management of adult aggressive non-Hodgkin's lymphomas.

    PubMed

    Couderc, B; Dujols, J P; Mokhtari, F; Norkowski, J L; Slawinski, J C; Schlaifer, D

    2000-07-01

    Aggressive non-Hodgkin's lymphona include diffuse large B-cell lymphoma, anaplastic large cell lymphona, and different peripheral T-cell lymphomas. An international prognostic index has been developed including age, serum LDH, performance status, and extranodal involvement. For localized aggressive lymphoma, the preferred treatment is 3-4 CHOP and radiation therapy, with a cure rate of 70-80%. For disseminated aggressive lymphoma, current regimens have a cure rate of less than 40%. Innovative strategies, including dose escalation, autologus stem cell support, new drugs, and immunotherapy are being explored to improve these results. PMID:10863150

  6. Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    PubMed Central

    Amann, Birgit H.

    2016-01-01

    Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when

  7. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    PubMed

    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. PMID:26892232

  8. Serotonin and Aggressiveness in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin (5-HT) regulates aggressive behavior in animals. This study examined if 5-HT regulation of aggressiveness is gene-dependent. Chickens from two divergently selected lines KGB and MBB (Kind Gentle Birds and Mean Bad Birds displaying low and high aggressiveness, respectively) and DXL (Dekalb ...

  9. Children's normative beliefs about aggression and aggressive behavior.

    PubMed

    Huesmann, L R; Guerra, N G

    1997-02-01

    Normative beliefs have been defined as self-regulating beliefs about the appropriateness of social behaviors. In 2 studies the authors revised their scale for assessing normative beliefs about aggression, found that it is reliable and valid for use with elementary school children, and investigated the longitudinal relation between normative beliefs about aggression and aggressive behavior in a large sample of elementary school children living in poor urban neighborhoods. Using data obtained in 2 waves of observations 1 year apart, the authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior. More important, although individual differences in aggressive behavior predicted subsequent differences in normative beliefs in younger children, individual differences in aggressive behavior were predicted by preceding differences in normative beliefs in older children. PMID:9107008

  10. Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial

    PubMed Central

    Lee, Myeong Soo; Lee, Jung-Sook

    2010-01-01

    We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

  11. Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial.

    PubMed

    Choi, Ae-Na; Lee, Myeong Soo; Lee, Jung-Sook

    2010-06-01

    We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

  12. Two Cases of Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients with Chronic Human Papillomavirus Infection

    PubMed Central

    Kuma, Yuki; Ito, Takamichi; Nagae, Konosuke; Mizote, Yukihiro; Nakahara, Takeshi; Uchi, Hiroshi; Yamada, Yuichi; Okura, Masae; Oda, Yoshinao; Yamashita, Toshiharu; Furue, Masutaka

    2015-01-01

    Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK. PMID:26351427

  13. Potential of immunosuppressive agents in cerebral ischaemia

    PubMed Central

    Gupta, Yogendra Kumar; Chauhan, Anjali

    2011-01-01

    Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia. PMID:21321416

  14. Immunosuppressant deoxyspergualin inhibits antigen processing in monocytes.

    PubMed

    Hoeger, P H; Tepper, M A; Faith, A; Higgins, J A; Lamb, J R; Geha, R S

    1994-11-01

    Deoxyspergualin (DSG) is a novel immunosuppressive agent recently shown to bind to the constitutive heat shock protein 70, which is involved in binding and intracellular transport of antigenic peptides. In this study, we show that DSG inhibits the proliferation of PBMCs to the Ags tetanus toxoid and diphtheria toxoid, but not to the mitogens PHA and PMA/ionomycin, nor to the superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxin A. DSG's effect was specific for monocytes as preincubation of T cells with DSG did not inhibit their proliferation to monocytes pulsed with tetanus toxoid Ag for 16 h, whereas the presence of DSG during Ag pulsing of the monocytes inhibited their ability to stimulate T cell proliferation. DSG did not down-regulate the expression of MHC class II molecules by monocytes, and the inhibitory effect of DSG on T cell proliferation was not reversed by the addition of IL-2, nor by the addition of the costimulatory signals IL-1, IL-6, and anti-CD28. Studies with two human T cell clones, HA1.7 and PF5, specific, respectively, to peptides spanning amino acids 307-319 and 256-270 of influenza hemagglutinin, showed that DSG inhibited the proliferation of the clones to the native hemagglutinin molecule but minimally affected their proliferation to the peptides. These data suggest that DSG interferes with Ag processing and/or presentation. PMID:7930603

  15. Immunosuppressive mechanisms in protein-calorie malnutrition

    SciTech Connect

    Redmond, H.P.; Shou, J.; Kelly, C.J.; Schreiber, S.; Miller, E.; Leon, P.; Daly, J.M. )

    1991-08-01

    Protein-calorie malnutrition (PCM) induces immunosuppression leading to increased mortality rates. Impaired macrophage respiratory burst activity (superoxide anion (O2-) generation) occurs in PCM, but cellular mechanisms are unclear. The major pathway resulting in O2- production involves inositol lipid-dependent signal transduction. This study examined the effect of mild versus severe PCM on macrophage O2- generating signal transduction pathways specific for responses to Candida albicans. Mice (CFW/Swiss Webster: n = 300) were randomized to either control or low protein diets for 3 or 8 weeks. Peritoneal macrophages were harvested for O2- production, mannose-fucose receptor (MFR) expression, membrane phospholipid analysis, arachidonic acid (AA) content, prostaglandin E2 (PGE2) production, and protein kinase C levels. O2- release was impaired in both mild and severe PCM. MFR expression was also decreased at these time points. Inositol lipid content was significantly lower at the 8-week time point only, although PGE2 and AA were significantly higher in the low protein diet group at 3 weeks. Protein kinase C levels were unchanged by PCM. Thus, mild PCM significantly increases macrophage-PGE2 production secondary to increased AA phospholipid content, with subsequent inhibition of O2- and MFR expression. Severe PCM inhibits macrophage (O2-) through depletion of critical membrane phospholipid components with subsequent impairment in signal transduction.

  16. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

    PubMed

    Salinas-Carmona, Mario Cesar; Rosas-Taraco, Adrian Geovanni; Welsh, Oliverio

    2012-10-01

    Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma. PMID:22825801

  17. The antigenic and immunosuppressive properties of normal and antilymphocytic equine IgG subfractions

    PubMed Central

    Allardyce, R. A.; Anderson, N. F.; Vaerman, J. P.; James, K.

    1973-01-01

    The antigenic and immunosuppressive properties of normal and antilympho-cytic equine globulin subfractions were investigated in the rat model in an attempt to increase the efficacy of prolonged ALG therapy by limiting the immunogenic stimulus of `inactive' subfractions. Chromatographic separation of equine IgG components yielded an electro-phoretically slow gamma 2 fraction consisting of IgG2a and IgG2b and a more heterogeneous fast gamma 1 subfraction. Immunosuppression resulting from the administration of isolated subfractions was measured by the response to alum-BSA and skin allograft survival. Antigenicity was determined by a variety of immunological procedures. The immunosuppressive character of the ALG was confined to the gamma 2 fraction, however this fraction also proved antigenic in our system. The administration of normal equine IgG subfractions in combination with Freund's complete adjuvant resulted in the demonstration of antigenic differences between the fast and slow IgG components. ImagesFig. 1Fig. 2 PMID:4120853

  18. Reversal of long-term sepsis-induced immunosuppression by dendritic cells

    PubMed Central

    Benjamim, Claudia F.; Lundy, Steven K.; Lukacs, Nicholas W.; Hogaboam, Cory M.; Kunkel, Steven L.

    2005-01-01

    Severe sepsis leads to long-term systemic and local immunosuppression, which is the cause of a number of complications, including pulmonary infection. A therapeutic strategy that reverses this immunosuppression is required, given the ongoing high mortality rate of patients who have survived a severe sepsis. The present study demonstrates that experimental severe sepsis renders the lung susceptible to a normally innocuous Aspergillus fumigatus fungus challenge, due to a dominant lung type 2 cytokine profile. Dendritic cells (DCs) obtained from the lungs of mice subjected to cecal ligation and puncture (CLP) model were skewed toward type 2 cytokine profile, which occurred with exaggerated expression of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone marrow–derived DCs (BMDCs) in postseptic mice prevented fatal Aspergillus infection. This therapy reduced the overall inflammatory response and fungal growth in the lung, and promoted the balance of proinflammatory and suppressive cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore the pulmonary host response in the postseptic lung in our animal model. These data strongly suggest that lung DCs are profoundly affected as a consequence of the systemic impact of severe sepsis, and the identification of mechanisms that restore their function may serve as a key strategy to reverse sepsis-induced immunosuppression. PMID:15604223

  19. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    SciTech Connect

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.S.

    1982-10-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

  20. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    SciTech Connect

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.L.

    1982-10-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

  1. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure

    PubMed Central

    Pattullo, Venessa

    2015-01-01

    Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations’ guidelines and the best available evidence to date. PMID:25954478

  2. [Investigation of Pneumocystis jirovecii pneumonia and colonization in iatrogenically immunosuppressed and immunocompetent patients].

    PubMed

    Özkoç, Soykan; Bayram Delibaş, Songül

    2015-04-01

    Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be detected in healthy individuals and in patients with various underlying lung diseases. The aim of this study was to evaluate the immunocompetent and iatrogenically immunosuppressed patients in terms of PCP and P.jirovecii colonization. A total of 92 patients (66 male, 26 female; age range: 18-93 years, median: 58.5) who underwent bronchoscopy due to various pulmonary symptoms between January 2011-April 2014, were included in the study. Of these patients, 65 were under immunosuppressive therapy (38 were treated with anti-cancer drugs, 15 with anti-rejection/immunomodulatory drugs and 12 with corticosteroids), while 27 were immunocompetent. Bronchoalveolar lavage (BAL) fluids were evaluated for the presence of P.jirovecii mitochondrial gene coding ribosomal large subunit (mtLSUrRNA) with nested PCR (nPCR) method. All of the samples were also examined by Giemsa and Gomori's methenamine silver (GMG) staining methods. P.jirovecii DNA was detected in 31 (33.7%) out of 92 BAL samples by nPCR. Although six immunosuppressed patients were positive in the first round of amplification, 26 of 65 (40%) immunosuppressed and five of 27 (18.5%) immunocompetent patients were positive with nPCR. P.jirovecii cysts and trophozoites were detected in only five (16.1%) of the 31 nPCR positive samples. The probability of being immunosuppressive among nPCR positive cases was statistically higher than nPCR negative cases (χ²= 3.940; p= 0.047). This difference was more significant in organ transplant recipients and patients under anti-rejection/immunomodulatory treatment (χ²= 6.715, p= 0.01; χ²= 5.550, p= 0.018, respectively). When clinical, laboratory and radiological findings of nPCR positive patients were considered, five patients (2 kidney transplant, 1 bone marrow transplant, 1 interstitial lung disease and 1 lung

  3. Motives in Sexual Aggression: The Chinese Context.

    ERIC Educational Resources Information Center

    Tang, Catherine So-Kum; And Others

    1993-01-01

    Compared sexual and aggressive motives for sexual aggression in Chinese college students. Male undergraduates (N=146) completed self-report measures. Results suggest that sex guilt and aggressive guilt acted as inhibitors for their respective drives and sexual aggression resulted from aggressive, rather than sexual, motives. Sexual aggression may…

  4. [Current status of oral immunomodulatory and immunosuppressive agents].

    PubMed

    Meller, S; Baran, A M; Braun, S A; Klossowski, N; Homey, B

    2014-02-01

    Various dermatological disorders require treatments with immunosuppressive or immunomodulatory agents. Nevertheless, several studies demonstrate low prescription rates for systemic treatments. This low usage may be a result of physicians' low levels of confidence in administering systemic treatments. However, immunosuppressive treatments represent safe options when potential side effects as well as pharmacological interactions are considered. This review overviews the most important oral immunosuppressive or immunomodulatory agents and summarizes their mode of actions, indications, and adverse effects. Biologics that require intravenous or subcutaneous application are not included, but novel and new agents likely to be released soon are considered. PMID:24549480

  5. Immune responses against islet allografts during tapering of immunosuppression - A pilot study in 5 subjects.

    PubMed

    Huurman, Volkert A L; van der Torren, Cornelis R; Gillard, Pieter; Hilbrands, Robert; van der Meer-Prins, Ellen P M W; Duinkerken, Gaby; Gorus, Frans K; Claas, Frans H J; Keymeulen, Bart; Roelen, Dave L; Pipeleers, Daniel G; Roep, Bart O

    2012-04-25

    Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (p=0.035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. PMID:23607493

  6. Immune responses against islet allografts during tapering of immunosuppression--a pilot study in 5 subjects.

    PubMed

    Huurman, V A L; van der Torren, C R; Gillard, P; Hilbrands, R; van der Meer-Prins, E P M W; Duinkerken, G; Gorus, F K; Claas, F H J; Keymeulen, B; Roelen, D L; Pipeleers, D G; Roep, B O

    2012-08-01

    Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (P = 0·035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity. PMID:22774994

  7. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    PubMed

    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. PMID:8100914

  8. Some transformations of tacrolimus, an immunosuppressive drug.

    PubMed

    Skytte, Dorthe M; Jaroszewski, Jerzy W; Johansen, Kenneth T; Hansen, Steen Honoré; Hansen, Liselotte; Nielsen, Peter G; Frydenvang, Karla

    2013-02-14

    Transformations of the macrocyclic lactone tacrolimus (1), an important immunosuppressive drug produced by Streptomyces species, are described. These transformation products are primarily of interest as reference substances for drug impurity analyses. Upon action of acid (p-toluenesulfonic acid in toluene), tacrolimus is dehydrated by loss of water from the β-hydroxyketone moiety with partial inversion of configuration at C-8, resulting in formation of 5-deoxy-Δ(5,6)-tacrolimus and 5-deoxy-Δ(5,6)-8-epitacrolimus. The structure of the latter was determined by single-crystal X-ray crystallography. The same products are formed upon action of free radicals (iodine in boiling toluene), along with formation of 8-epitacrolimus. The latter is converted by p-toluenesulfonic acid to 5-deoxy-Δ(5,6)-8-epitacrolimus. Treatment of tacrolimus with weak base (1,5-diazabicyclo[4.3.0]nonene) gives, in addition to 8-epitacrolimus, the open-chain acid corresponding to 5-deoxy-Δ(5,6)-tacrolimus, a rare non-cyclic derivative of tacrolimus. Strong base (t-butoxide) causes pronounced degradation of the molecule. Thermolysis of tacrolimus leads to ring expansion by an apparent [3,3]-sigmatropic rearrangement of the allylic ester moiety with subsequent loss of water from the β-hydroxyketone moiety. ¹H and ¹³C NMR spectra of the obtained compounds, complicated by the presence of amide bond rotamers and ketal moiety tautomers, were assigned by extensive use of 2D NMR techniques. PMID:23238171

  9. Lung transplant immunosuppression – time for a new approach?

    PubMed Central

    Witt, CA; Puri, V; Gelman, AE; Krupnick, AS; Kreisel, D

    2015-01-01

    Summary Outcomes after lung transplantation remain worse compared to other solid organ transplants, which is in large part due to high rates of graft rejection. Despite emerging data that immune responses to lungs differ from other organs, immunosuppression for lung transplant recipients is still based on strategies established for recipients of other grafts. There exists an urgent need to develop immunosuppressive strategies for lung transplant recipients that take the unique immunological features of this organ into account. PMID:25220652

  10. Effectiveness of ECT combined with risperidone against aggression in schizophrenia.

    PubMed

    Hirose, S; Ashby, C R; Mills, M J

    2001-03-01

    Aggressive behavior in schizophrenic patients can often be problematic not only for the patients themselves, but for their families and others. This study examined the effect of electroconvulsive therapy (ECT) in combination with risperidone in an open trial in 10 male schizophrenic patients with significant aggressive behaviors. Patients were given bilateral ECT five times a week in combination with risperidone. The mean total number of times of ECT was 6.6 (range 5-9). The aggressive behavior in five of the six patients, who showed positive symptoms, was rapidly ameliorated within 12 days. The ECT/risperidone regimen also eliminated aggressive behavior in four patients showing no positive symptoms within 10 days. These treatment effects lasted for at least 6 months in 9 (of the 10) patients. The results suggest that ECT, combined with risperidone, produce a rapid and effective elimination of aggressive behaviors in schizophrenic patients. In addition, there was a resolution of aggression in four patients with no positive symptoms. This suggests that aggression in some schizophrenic patients develops as a primary symptom of schizophrenia and is not related to other positive symptoms of the disease or the patient's personality traits. PMID:11281510

  11. Effect of Increased Immunosuppression on Developmental Outcome of Opsoclonus Myoclonus Syndrome (OMS).

    PubMed

    Mitchell, Wendy G; Wooten, Amelia A; O'Neil, Sharon H; Rodriguez, Jenny G; Cruz, Rosa E; Wittern, Rachael

    2015-07-01

    Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal. PMID:25342308

  12. The nature of human aggression.

    PubMed

    Archer, John

    2009-01-01

    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making. PMID:19411108

  13. Girls, aggression, and emotion regulation.

    PubMed

    Conway, Anne M

    2005-04-01

    Many studies have demonstrated that boys are more aggressive than girls (see J. D. Coie & K. Dodge, 1997, for a review) and that emotion regulation difficulties are associated with problematic behaviors (N. Eisenberg & R. A. Fabes, 1999; M. Gilliom, D. S. Shaw, J. E. Beck, M. A. Schonberg, & J. L. Lukon, 2002). However, recent findings indicate that gender differences in aggressive behaviors disappear when assessments are broadened to include relational aggression--behaviors designed to harm the relationship goals of others by spreading rumors, gossiping, and eliciting peer rejection of others. Moreover, although difficulties regulating emotions have been reported for physically aggressive children, little research has examined these processes in relationally aggressive children. This article argues that investigation into the associations between emotion regulation and relational aggression is a critical direction for future research on the etiology and prevention of mental health problems in girls. PMID:15839769

  14. Chronic Phototoxicity and Aggressive Squamous Cell Carcinoma of the Skin in Children and Adults During Treatment with Voriconazole

    PubMed Central

    Cowen, Edward W.; Nguyen, Josephine C.; Miller, Daniel D.; McShane, Diana; Arron, Sarah T.; Prose, Neil S.; Turner, Maria L.; Fox, Lindy P.

    2009-01-01

    Background Voriconazole is a broad spectrum antifungal agent associated with photosensitivity and accelerated photoaging. A possible link with aggressive squamous cell carcinoma (SCC) has also been reported. Objective To determine the incidence and frequency of cutaneous SCC amongst patients undergoing long-term treatment with voriconazole who also manifest features of chronic phototoxicity. Methods A retrospective review of patients who developed one or more squamous cell neoplasms during long-term treatment with voriconazole at three academic dermatology centers. Results 51 cutaneous SCC were identified in 8 patients (median age 34.5 years, range 9–54) treated with chronic voriconazole (median duration 46.5 months, range 13–60). Underlying diagnoses included graft-versus-host disease, HIV, and Wegener’s granulomatosis. Signs of chronic phototoxicity and accelerated photoaging included erythema, actinic keratoses, and lentigo formation. Limitations The retrospective nature of the study cannot determine the true population risk of SCC associated with voriconazole therapy. A prospective cohort study is needed. Conclusion A high index of suspicion for photosensitivity and SCC may be warranted with chronic voriconazole use when utilized in the setting of concurrent immunosuppression. PMID:19896749

  15. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    PubMed Central

    Cao, Yuan; Zhao, Di; Xu, An-Tao; Shen, Jun; Ran, Zhi-Hua

    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 “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

  16. Rethinking Aggression: A Typological Examination of the Functions of Aggression.

    ERIC Educational Resources Information Center

    Little, Todd D.; Brauner, Jessica; Jones, Stephanie M.; Nock, Matthew K.; Hawley, Patricia H.

    2003-01-01

    Compared five subgroups of aggressive children and adolescents on several adjustment correlates. Found that the reactive group and the group high on both instrumental and reactive reasons for aggression showed consistent maladaptive patterns across the adjustment correlates. The instrumental and typical groups (moderate on instrumental and…

  17. Aggression, suicidality, and serotonin.

    PubMed

    Linnoila, V M; Virkkunen, M

    1992-10-01

    Studies from several countries, representing diverse cultures, have reported an association between violent suicide attempts by patients with unipolar depression and personality disorders and low concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Related investigations have documented a similar inverse correlation between impulsive, externally directed aggressive behavior and CSF 5-HIAA in a subgroup of violent offenders. In these individuals, low CSF 5-HIAA concentrations are also associated with a predisposition to mild hypoglycemia, a history of early-onset alcohol and substance abuse, a family history of type II alcoholism, and disturbances in diurnal activity rhythm. These data are discussed in the context of a proposed model for the pathophysiology of a postulated "low serotonin syndrome." PMID:1385390

  18. Clinical and radiological features of brain neurotoxicity caused by antitumor and immunosuppressant treatments.

    PubMed

    Erbetta, Alessandra; Salmaggi, Andrea; Sghirlanzoni, Angelo; Silvani, Antonio; Potepan, Paolo; Botturi, Andrea; Ciceri, Elisa; Bruzzone, Maria Grazia

    2008-06-01

    Antitumor and immunosuppressant treatment-related neurotoxicity can determine nonspecific clinical syndromes. Exclusion of other possible causes, among which tumor progression, appearance of paraneoplastic disease, renal or hepatic failure, diabetes or hypertension, is relevant. We report clinical and neuroradiological features in five patients with neurotoxic syndromes due to chemotherapy/radiotherapy or immunosuppression in the context of neoplastic disease/organ transplantation. Acute neurological syndrome developed in three patients after methotrexate (MTX), cyclosporine A, and L-asparaginase therapy, respectively. MRI showed posterior reversible encephalopathy in two cases and venous thrombosis with intraparenchymal hematoma in the third patient. Late onset clinical syndrome occurred in the last two patients, treated with MTX or radiation therapy for breast cancer metastasis and pituitary adenoma. Neuroimaging showed brain diffuse abnormalities. Patients affected by tumors suffer from increased risk for treatment-related toxicities. Appearance or worsening of neurological signs and symptoms challenge the clinician to discriminate between CNS involvement by the tumor, toxicity of drugs, parane-oplastic disease and infections. MRI has a key role in differential diagnosis. Close interaction between the neurologist, the oncologist and the neuroradiologist leads to the optimal management of patients. PMID:18612759

  19. The Effects of Pornography on Aggressive Behavior.

    ERIC Educational Resources Information Center

    Stacy, Lauri L.

    This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…

  20. Subtypes of Aggressive Behaviors: A Developmental Perspective

    ERIC Educational Resources Information Center

    Vitaro, Frank; Brendgen, Mara; Barker, Edward D.

    2006-01-01

    Aggressive behaviors in children and adolescents have undergone important conceptual and definitional modifications in the past two decades. In particular, subtypes of aggression have been proposed that separate the form and the function of the aggressive behaviors (i.e., social vs. physical aggression; reactive vs. proactive aggression).…

  1. Psychological Research on Human Aggressiveness

    ERIC Educational Resources Information Center

    Hamburg, D. A.; Brodie, H. K. H.

    1973-01-01

    Discusses research relating to the effects of hormones, neurophysiology, and the environment on animal and human aggression. Indicates that the interactions of biological, psychological and social processes in the development of human aggressiveness should constitute one of the principal frontiers for science in the next two decades. (JR)

  2. Aggression and Violence in Youth.

    ERIC Educational Resources Information Center

    William Gladden Foundation, York, PA.

    This booklet was written to provide an understanding of aggression and violence in youth. Its purpose is to help parents, professionals, and other concerned citizens prevent or reduce these potentially dangerous behaviors. The introduction notes that many experts agree that aggression and violence are on the rise in America. The first section of…

  3. Lunar Influences on Human Aggression.

    ERIC Educational Resources Information Center

    Russell, Gordon W.; Dua, Manjula

    1983-01-01

    Used league records of all Canadian hockey games (N=426) played during a season to test a lunar-aggression hypothesis. Despite the use of multiple measures of lunar phase and interpersonal aggression, support for lunar influence was not forthcoming. Supplemental data revealed that beliefs in lunar influence are fairly common. (JAC)

  4. A psychoanalytic study of aggression.

    PubMed

    Furst, S S

    1998-01-01

    Eleven participants carried out a study of aggression by utilizing clinical data from the analyses of patients who manifested significant problems in the management of aggression. The purpose of the study was to increase understanding of the intrapsychic factors that determine the nature and intensity of aggressive tendencies, the place they occupy in the psychic economy, their patterns of expression, and the extrapsychic factors that trigger them. The findings of the study indicate, first, that aggression is multiply determined by developmental, genetic (experiential), and dynamic variables; second, that each cluster of variables affects the nature, intensity, and expression of aggression in a fairly specific way; third, the importance of aggression in the psychic economy is proportional to the extent to which it is overdetermined. The successful analysis of aggressive individuals depends not solely on interpretation and insight, but on the relationship to the analyst as new parent who does not threaten and prohibit. The relationship to the analyst permits developmental change, particularly the ability to organize, structure, and control aggression. As a result, it need not be expressed destructively, but may be placed in the service of constructive thought and action. PMID:9990829

  5. Fingerprints of transplant tolerance suggest opportunities for immunosuppression minimization.

    PubMed

    Sarwal, Minnie M

    2016-03-01

    HLA incompatible organ transplant tolerance is the holy grail of transplantation. Stable engraftment of an HLA mismatched allograft and life-long tolerance induction, though feasible in highly selected cohorts with depletional protocols, is not ready for generalized application to the entire transplant recipient pool. It has thus been important to harness biomarkers that can uncover mechanisms and tools for monitoring HLA mismatched recipients that develop a state of operational tolerance, during accidental immunosuppression withdrawal secondary to problems of over-immunosuppression (infection or malignancy) or toxicity (mostly cosmetic or cardiovascular). A restricted and unpredictable group of patients can demonstrate a clinical state of operational tolerance, manifested by state of stable graft function of a graft with HLA mismatches between recipient and donor, intact immune responses to third party antigens and no measurable immunosuppression. These patients have served as the basis for the discovery of clinically correlative biomarkers, in distal biofluids (mainly blood), that can define the existing state of operational clinical tolerance. Operationally tolerant patients are rare, as withdrawal of immunosuppression most often results in rejection and graft loss. Nevertheless, operationally tolerant kidney, liver and heart allograft recipients have been reported. The presence of similar biomarker signature profiles in HLA mismatched transplant recipients on immunosuppression, suggests the feasibility of utilizing these biomarkers for educated immunosuppression minimization with a view to retaining immunological quiescence, while reducing the maintenance immunosuppression burden to a "safe" alloimmune threshold. Though clinical operational tolerance is rare, as immunosuppression cessation most often results in increased alloimmunity and rejection, the biomarker profile studies that have harnessed whole genome profiling suggest that the frequency of this state

  6. In search of Winnicott's aggression.

    PubMed

    Posner, B M; Glickman, R W; Taylor, E C; Canfield, J; Cyr, F

    2001-01-01

    Going beyond Winnicott's widely known ideas about creativity, in this paper the authors ask why some people are able to live creatively while others suffer recurrent feelings of anger, futility, and depression. Examining Winnicott's reframing of aggression as a life force, it attempts to answer this question by tracing the evolution of his thinking on the nature and origin of aggression. It argues that because he saw aggression as inherent and as central to emotional development, interference in its expression compromises psychic maturation. The paper explores how Winnicott arrived at the conception of a combined love-strife drive and demonstrates that for him, there is no love without aggression, no subject, no object, no reality, and no creativity. That is, for Winnicott, aggression is an achievement that leads to the capacity to live creatively and to experience authenticity. Clinical vignettes illustrate the therapeutic use of these conclusions and their value for psychoanalytic theory. PMID:12102012

  7. False memories for aggressive acts.

    PubMed

    Laney, Cara; Takarangi, Melanie K T

    2013-06-01

    Can people develop false memories for committing aggressive acts? How does this process compare to developing false memories for victimhood? In the current research we used a simple false feedback procedure to implant false memories for committing aggressive acts (causing a black eye or spreading malicious gossip) or for victimhood (receiving a black eye). We then compared these false memories to other subjects' true memories for equivalent events. False aggressive memories were all too easy to implant, particularly in the minds of individuals with a proclivity towards aggression. Once implanted, the false memories were indistinguishable from true memories for the same events, on several dimensions, including emotional content. Implications for aggression-related memory more generally as well as false confessions are discussed. PMID:23639921

  8. An Empirical "Real World" Comparison of Two Treatments with Aggressive Adolescent Males

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Siv, Alexander M.; Matteson, Susan C.

    2005-01-01

    This research study compares the efficacy of Mode Deactivation Therapy (MDT), an advanced form of Cognitive Behavioral Therapy based on Beck's theory of modes, and standard Cognitive Behavioral Therapy (CBT) for adolescent males in residential treatment. The results showed MDT was superior to CBT in reducing both physical and sexual aggression and…

  9. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): A new phenotype of multiple organ failure

    PubMed Central

    Rosenthal, Martin D.; Moore, Frederick A.

    2015-01-01

    A new phenotype of multiple organ failure has appeared: Persistent Inflammatory, Immunosuppressed, Catabolic Syndrome (PICS). Comorbidities and age >65 years have been established as the leading risk factors for PICS. As the percentage of elderly people continues to increase the prevalence of PICS in our ICUs will surely grow. Malnutrition (despite appropriate supplementation), recurrent nosocomial infections, frailty, ventilator dependence, and an indolent death depicts the central theme that plagues PICS patients. Aligned with the recently awarded P50 grant by NIGMS entitled, “PICS: A New Horizon for Surgical Critical Care”, and the University Of Florida’s Sepsis and Critical Illness Research Center will investigate the genetic make-up of PICS patients, better understand frailty and the implication in trauma patients, and hopefully elucidate new therapies. Currently, there are no therapies to combat PICS aside from nutritional inference elaborated after reviewing the literature on Burns, Cachexia, and Sarcopenia. PMID:26086042

  10. Ultraviolet-induced alloantigen-specific immunosuppression in transplant immunity

    PubMed Central

    Hori, Tomohide; Kuribayashi, Kagemasa; Saito, Kanako; Wang, Linan; Torii, Mie; Uemoto, Shinji; Iida, Taku; Yagi, Shintaro; Kato, Takuma

    2015-01-01

    After the first observation of the immunosuppressive effects of ultraviolet (UV) irradiation was reported in 1974, therapeutic modification of immune responses by UV irradiation began to be investigated in the context immunization. UV-induced immunosuppression is via the action of regulatory T cells (Tregs). Antigen-specific Tregs were induced by high-dose UV-B irradiation before antigen immunization in many studies, as it was considered that functional alteration and/or modulation of antigen-presenting cells by UV irradiation was required for the induction of antigen-specific immunosuppression. However, it is also reported that UV irradiation after immunization induces antigen-specific Tregs. UV-induced Tregs are also dominantly transferable, with interleukin-10 being important for UV-induced immunosuppression. Currently, various possible mechanisms involving Treg phenotype and cytokine profile have been suggested. UV irradiation accompanied by alloantigen immunization induces alloantigen-specific transferable Tregs, which have potential therapeutic applications in the transplantation field. Here we review the current status of UV-induced antigen-specific immunosuppression on the 40th anniversary of its discovery. PMID:25815267

  11. Adverse Effects of Systemic Immunosuppression in Keratolimbal Allograft

    PubMed Central

    Krakauer, M.; Welder, J. D.; Pandya, H. K.; Nassiri, N.; Djalilian, A. R.

    2012-01-01

    Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities. PMID:22523651

  12. Predicting aggressive behavior with the aggressiveness-IAT.

    PubMed

    Banse, Rainer; Messer, Mario; Fischer, Ilka

    2015-01-01

    The Implicit Association Test (IAT, Greenwald, McGhee, & Schwartz, 1998) was adapted to assess the automatically activated (implicit) self-concept of aggressiveness. In three studies the validity of the Aggressiveness-IAT (Agg-IAT) was supported by substantial correlations with self-report measures of aggressiveness. After controlling for self-report measures of aggressiveness, the Agg-IAT accounted for 9-15% of the variance of three different indicators of aggressive behavior across three studies. To further explore the nomological network around the Agg-IAT we investigated its correlations with measures of social desirability (SD). Although not fully conclusive, the results across four studies provided some support for a weak negative correlation between impression management SD and aggressive behavior as well as the Agg-IAT. This result is in line with an interpersonally oriented self-control account of impression management SD. Individuals with high SD scores seem to behave less aggressively, and to show lower Agg-IAT scores. The one-week stability of the Agg-IAT was r = .58 in Study 4. Aggr. Behav. 41:65-83 2015. © 2014 Wiley Periodicals, Inc. PMID:27539875

  13. Instrumental and Social Outcome Expectations of High-Aggressive and Low-Aggressive Boys.

    ERIC Educational Resources Information Center

    Cillessen, Antonius H. N.; Hubbard, Julie A.

    This study examined high-aggressive and low-aggressive boys' ratings of the effectiveness of aggressive and assertive strategies for solving social problems involving hypothetical peers and actual peers. Subjects were 66 third-grade boys (11 groups of 6 boys each for a total of 22 high-aggressive, 22 low-aggressive, and 22 average aggressive boys)…

  14. Aggressive Erotica and Violence against Women.

    ERIC Educational Resources Information Center

    Donnerstein, Edward

    1980-01-01

    Examines the effects of aggressive-erotic stimuli on male aggression toward females. Male subjects' deliveries of electric shocks to males or females after viewing either a neutral, erotic, or aggressive-erotic film were measured. (Author/SS)

  15. Septic arthritis in the era of immunosuppressive treatments.

    PubMed

    Salar, O; Baker, B; Kurien, T; Taylor, A; Moran, C

    2014-03-01

    Immunosuppressants have been the mainstay of treatment for certain inflammatory joint conditions for many years. Developments in this field, namely biological treatments, have led to a change in the classical presentation of acute bone, joint and soft tissue infections. The normal findings of severe pain and tenderness on examination may be absent or simply mimic a typical exacerbation of the chronic joint condition. A minimally raised white cell count and elevated C-reactive protein in the absence of systemic signs of infection may be interpreted as further evidence for the diagnosis of an exacerbation of inflammatory arthritis. We present a unique case of recurrent polyarticular septic arthritis in a patient treated with immunosuppression for refractory rheumatoid arthritis. We hope this article will enable doctors to appreciate and recognise the changing face of septic arthritis in the modern era of immunosuppressant treatments. PMID:24780657

  16. In vitro study of immunosuppressive effect of apoptotic cells*

    PubMed Central

    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. PMID:16130196

  17. Prolonged treatment response in aggressive natural killer cell leukemia.

    PubMed

    Osuji, N; Matutes, E; Morilla, A; Del Giudice, I; Wotherspoon, A; Catovsky, D

    2005-05-01

    We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly. The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis. Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow). The subsequent clinical course has been indolent, but this may have been influenced by treatment. Treatment consisted sequentially of splenectomy, intravenous pentostatin and the combination of cyclosporine A and recombinant human erythropoietin and has resulted in survival of over 48 months. We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders. PMID:16019515

  18. A new potent immunosuppressive isoflavanonol from Campylotropis hirtella.

    PubMed

    Xuan, Bixia; Du, Xing; Li, Xiaoping; Shen, Zhengwu

    2016-06-01

    Four new flavonoids were isolated from Campylotropis hirtella and these are a chromone and a 2H-chromene, an isoflavone and an isoflavanonol. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Compound 4 showed very strong T lymphocyte suppression activity (IC50: 0.13 μM) and potent B lymphocyte suppression activity (IC50: 0.26 μM). Due to its potent immunosuppressive activity and lower cytotoxicity, further structure-activity studies will be pursued on this compound. PMID:26221996

  19. An Aggressive Retroperitoneal Fibromatosis

    PubMed Central

    Campara, Zoran; Spasic, Aleksandar; Aleksic, Predrag; Milev, Bosko

    2016-01-01

    Introduction: Aggressive fibromatosis (AF) is a heterogeneous group of mesenchymal tumors that have locally infiltrative growth and a tendency to relapse. The clinical picture is often conditioned by the obstruction of the ureter or small intestine. Diagnosis is based on clinical, radiological and histological parameters. A case report: We report a case of male patient, aged 35 years, with the retroperitoneal fibromatosis. He reported to the physician because of frequent urination with the feeling of pressure and pain. Computed tomography revealed the tumor mass on the front wall of the bladder with diameter of 70mm with signs of infiltration of the musculature of the anterior abdominal wall. Endoscopic transurethral biopsy showed proliferative lesion binders by type of fibromatosis. The tumor was surgically removed in a classical way. The patient feels well and has no recurrence thirty-six months after the operative procedure. Conclusion: The complete tumor resection is the therapeutic choice for the primary tumor as well as for a relapse. PMID:27147794

  20. [The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation].

    PubMed

    Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Moreira, Marcos Aurélio; Marchiori, Paulo Eurípedes; Bacheschi, Luiz Alberto; Arruda, Walter Oleschko; Campos, Gilberto Belisário; Lino, Angelina Maria Martins; Melo, Aílton Souza; Rocha, Fernando Coronetti Gomes; Ferreira, Maria Lúcia Brito; Ataide, Luiz; Maciel, Damacio Ramón Kaimen

    2002-09-01

    Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to support the guidelines expressed in the BCTRIMS Expanded Consensus on Treatment of MS. PMID:12364965

  1. Genetics of Aggression in Voles

    PubMed Central

    Gobrogge, Kyle L.; Wang, Zuoxin

    2016-01-01

    Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form pair bonds—a behavior composed of several social interactions including attachment with a familiar mate and aggression toward conspecific strangers. Therefore, this species has provided an excellent opportunity for the study of pair bonding behavior and its underlying neural mechanisms. In this chapter, we discuss the utility of this unique animal model in the study of aggression and review recent findings illustrating the neurochemical mechanisms underlying pair bonding-induced aggression. Implications of this research for our understanding of the neurobiology of human violence are also discussed. PMID:22078479

  2. Predicting workplace aggression and violence.

    PubMed

    Barling, Julian; Dupré, Kathryne E; Kelloway, E Kevin

    2009-01-01

    Consistent with the relative recency of research on workplace aggression and the considerable media attention given to high-profile incidents, numerous myths about the nature of workplace aggression have emerged. In this review, we examine these myths from an evidence-based perspective, bringing greater clarity to our understanding of the predictors of workplace aggression. We conclude by pointing to the need for more research focusing on construct validity and prevention issues as well as for methodologies that minimize the likelihood of mono-method bias and that strengthen the ability to make causal inferences. PMID:18793089

  3. Non-Hodgkin's Malignant Lymphoma with Aggressive Development

    PubMed Central

    DANCIU, Cezara Elisabeta; HEROIU (CATALOIU), Adriana-Daniela; POPESCU, Cristian Radu

    2014-01-01

    Non-Hodgkin's malignant lymphoma is a hematologic malignant disease which usually responds to the polychemotherapy. We present a clinical case report of a 50 years old patient who develops an aggressive type of lymphoma. Patient develops a nodal Non-Hodgkin's malignant lymphoma who present at hospital admission as a huge tumor at the right side of the neck. Any type of treatment was a failure, the patient having a particularly aggressive form of lymphoma, resistant to all three chemotherapy regimens tested. Death occurs quickly, about one year after diagnosis and initiation of therapy. PMID:25553129

  4. Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation.

    PubMed

    Pratschke, Johann; Dragun, Duska; Hauser, Ingeborg A; Horn, Sabine; Mueller, Thomas F; Schemmer, Peter; Thaiss, Friedrich

    2016-04-01

    The wide range of immunosuppressive therapies and protocols permits tailored planning of the initial regimen according to the immunological risk status of individual patients. Pre-transplant risk assessment can include many factors, but there is no clear consensus on which parameters to take into account, and their relative importance. In general younger patients are known to be at higher risk for acute rejection, compounded by higher rates of non-adherence in adolescents. Donor age and recipient gender do not appear to exert a meaningful effect on risk of rejection per se, but black recipient ethnicity remains a well-established risk factor even under modern immunosuppression regimens. Little difference in risk is now observed between deceased- and living-donor recipients. Immunological risk assessment has developed substantially in recent years. Cross-match testing with cytotoxic analysis has long been supplemented by flow cytometry, but development of solid-phase single-bead antigen testing of solubilized human leukocyte antigens (HLA) to detect donor-specific antibodies (DSA) permits a far more nuanced stratification of immunological risk status, including the different classes and intensities of HLA antibodies Class I and/or II, including HLA-DSA. Immunologic risk evaluation is now often based on a combination of these tests, but other assessments are becoming more widely introduced, such as measurement of non-HLA antibodies against angiotensin type 1 (AT1) receptors or T-cell ELISPOT assay of alloantigen-specific donor. Targeted densensitization protocols can improve immunological risk, notably for DSA-positive patients with negative cytotoxicity and flow cross-match. HLA mismatch remains an important and undisputed risk factor for rejection. Delayed graft function also increases the risk of subsequent acute rejection, and the early regimen can be modified in such cases. Overall, there is a shift towards planning the immunosuppressive regimen based on pre

  5. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

    PubMed Central

    Sagnelli, Evangelista; Pisaturo, Mariantonietta; Martini, Salvatore; Filippini, Pietro; Sagnelli, Caterina; Coppola, Nicola

    2014-01-01

    Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI. PMID:25018849

  6. Outcome of Hepatitis E Virus Infection in Patients With Inflammatory Arthritides Treated With Immunosuppressants

    PubMed Central

    Bauer, Hélène; Luxembourger, Cécile; Gottenberg, Jacques-Eric; Fournier, Sophie; Abravanel, Florence; Cantagrel, Alain; Chatelus, Emmanuel; Claudepierre, Pascal; Hudry, Christophe; Izopet, Jacques; Fabre, Sylvie; Lefevre, Guillaume; Marguerie, Laurent; Martin, Antoine; Messer, Laurent; Molto, Anna; Pallot-Prades, Béatrice; Pers, Yves-Marie; Roque-Afonso, Anne-Marie; Roux, Christian; Sordet, Christelle; Soubrier, Martin; Veissier, Claire; Wendling, Daniel; Péron, Jean-Marie; Sibilia, Jean

    2015-01-01

    Abstract The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2–20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3–55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure. PMID:25860212

  7. Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population.

    PubMed

    Szabó, Enikő; Fajka-Boja, Roberta; Kriston-Pál, Éva; Hornung, Ákos; Makra, Ildikó; Kudlik, Gyöngyi; Uher, Ferenc; Katona, Róbert László; Monostori, Éva; Czibula, Ágnes

    2015-09-15

    When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed-type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2≥MSC5>MSC4>MSC3 > MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN-γ and TNF-α resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions. PMID:26153898

  8. A SYNDROME OF SEVERE HYPOGLYCEMIA AND ACIDOSIS IN YOUNG IMMUNOSUPPRESSED DIABETIC MONKEYS AND PIGS – ASSOCIATION WITH SEPSIS1

    PubMed Central

    Zhou, Hao; van der Windt, Dirk J.; Dons, Eefje M.; Rigatti, Lora H.; Echeverri, Gabriel J.; Bottino, Rita; Wijkstrom, Martin; Wagner, Robert; Cooper, David K.C.

    2012-01-01

    Background Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes in these animals if islet transplantation is planned. Methods We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy +/− islet allotransplantation. Results In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe this syndrome has been reported previously by others. Conclusions Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function, and resulted in death or the need for euthanasia in all 7 animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate. PMID:23128998

  9. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    patient who underwent en bloc resection who continued to have back pain. CONCLUSIONS Gross-total resection or subtotal resection in combination with vertebroplasty or adjuvant radiation therapy to treat residual tumor seems sufficient in the treatment of aggressive vertebral hemangiomas. En bloc resection appears to provide a similar oncological benefit, but it carries higher morbidity to the patient. PMID:27476849

  10. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    PubMed

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  11. Mesenchymal stem cell secretome and regenerative therapy after cancer

    PubMed Central

    Zimmerlin, Ludovic; Park, Tea Soon; Zambidis, Elias T.; Donnenberg, Vera S.; Donnenberg, Albert D.

    2013-01-01

    Cancer treatment generally relies on tumor ablative techniques that can lead to major functional or disfiguring defects. These post-therapy impairments require the development of safe regenerative therapy strategies during cancer remission. Many current tissue repair approaches exploit paracrine (immunomodulatory, pro-angiogenic, anti-apoptotic and pro-survival effects) or restoring (functional or structural tissue repair) properties of mesenchymal stem/stromal cells (MSC). Yet, a major concern in the application of regenerative therapies during cancer remission remains the possible triggering of cancer recurrence. Tumor relapse implies the persistence of rare subsets of tumor-initiating cancer cells which can escape anti-cancer therapies and lie dormant in specific niches awaiting reactivation via unknown stimuli. Many of the components required for successful regenerative therapy (revascularization, immunosuppression, cellular homing, tissue growth promotion) are also critical for tumor progression and metastasis. While bidirectional crosstalk between tumorigenic cells (especially aggressive cancer cell lines) and MSC (including tumor stroma-resident populations) has been demonstrated in a variety of cancers, the effects of local or systemic MSC delivery for regenerative purposes on persisting cancer cells during remission remain controversial. Both pro- and anti-tumorigenic effects of MSC have been reported in the literature. Our own data using breast cancer clinical isolates have suggested that dormant-like tumor-initiating cells do not respond to MSC signals, unlike actively dividing cancer cells which benefited from the presence of supportive MSC. The secretome of MSC isolated from various tissues may partially diverge, but it includes a core of cytokines (i.e. CCL2, CCL5, IL-6, TGFβ, VEGF), which have been implicated in tumor growth and/or metastasis. This article reviews published models for studying interactions between MSC and cancer cells with a focus

  12. Environmental factors and aggressive behavior

    SciTech Connect

    Anderson, A.C.

    1982-07-01

    This paper briefly reviews some of the research areas which indicate a correlation between environmental factors and initiation of aggressive behavior. Environmental factors including lunar influences, month of birth, climate and the effects of crowding and certain chemicals are discussed.

  13. Quantifying Aggressive Behavior in Zebrafish.

    PubMed

    Teles, Magda C; Oliveira, Rui F

    2016-01-01

    Aggression is a complex behavior that influences social relationships and can be seen as adaptive or maladaptive depending on the context and intensity of expression. A model organism suitable for genetic dissection of the underlying neural mechanisms of aggressive behavior is still needed. Zebrafish has already proven to be a powerful vertebrate model organism for the study of normal and pathological brain function. Despite the fact that zebrafish is a gregarious species that forms shoals, when allowed to interact in pairs, both males and females express aggressive behavior and establish dominance hierarchies. Here, we describe two protocols that can be used to quantify aggressive behavior in zebrafish, using two different paradigms: (1) staged fights between real opponents and (2) mirror-elicited fights. We also discuss the methodology for the behavior analysis, the expected results for both paradigms, and the advantages and disadvantages of each paradigm in face of the specific goals of the study. PMID:27464816

  14. Neurotensin inversely modulates maternal aggression.

    PubMed

    Gammie, S C; D'Anna, K L; Gerstein, H; Stevenson, S A

    2009-02-18

    Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT's role in maternal defense. Intracerebroventricular (i.c.v.) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 microg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 microg) relative to vehicle, suggesting specificity of NT action on defense. Further, i.c.v. injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 microg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 microg NT or vehicle. Thirteen of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. PMID:19118604

  15. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  16. Black Dot Tinea Capitis in an Immunosuppressed Man

    PubMed Central

    Mendese, Gary W.; Loo, Daniel S.

    2013-01-01

    Tinea capitis is a common superficial fungal infection of the scalp primarily afflicting young children. In adults, this infection may have an atypical presentation that may lead to a delay in diagnosis. The authors present a case report of black dot tinea capitis in an immunosuppressed Asian man with psoriasis and provide a review of the literature. PMID:23710273

  17. The transcription factor BACH2 promotes tumor immunosuppression.

    PubMed

    Roychoudhuri, Rahul; Eil, Robert L; Clever, David; Klebanoff, Christopher A; Sukumar, Madhusudhanan; Grant, Francis M; Yu, Zhiya; Mehta, Gautam; Liu, Hui; Jin, Ping; Ji, Yun; Palmer, Douglas C; Pan, Jenny H; Chichura, Anna; Crompton, Joseph G; Patel, Shashank J; Stroncek, David; Wang, Ena; Marincola, Francesco M; Okkenhaug, Klaus; Gattinoni, Luca; Restifo, Nicholas P

    2016-02-01

    The immune system has a powerful ability to recognize and kill cancer cells, but its function is often suppressed within tumors, preventing clearance of disease. Functionally diverse innate and adaptive cellular lineages either drive or constrain immune reactions within tumors. The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its role in controlling tumor immunity has not been elucidated. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. However, augmented tumor clearance in the absence of Bach2 was dependent upon the adaptive immune system. Analysis of tumor-infiltrating lymphocytes from Bach2-deficient mice revealed high frequencies of rapidly proliferating effector CD4+ and CD8+ T cells that expressed the inflammatory cytokine IFN-γ. Effector T cell activation coincided with a reduction in the frequency of intratumoral Foxp3+ Tregs. Mechanistically, BACH2 promoted tumor immunosuppression through Treg-mediated inhibition of intratumoral CD8+ T cells and IFN-γ. These findings demonstrate that BACH2 is a key component of the molecular program of tumor immunosuppression and identify therapeutic targets for the reversal of immunosuppression in cancer. PMID:26731475

  18. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    SciTech Connect

    Goldberg, D.R.; Yuill, T.M.; Burgess, E.C. )

    1990-07-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  19. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    USGS Publications Warehouse

    Goldberg, D.R.; Yuill, Thomas M.; Burgess, E.C.

    1990-01-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  20. Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation.

    PubMed

    Hadamitzky, Martin; Engler, Harald; Schedlowski, Manfred

    2013-03-01

    Behavioral conditioning of immune responses is one of the most impressive examples for the bidirectional communication among the nervous and immune systems. We established a model of behaviorally conditioned immunosuppression employing a conditioned taste aversion (CTA) paradigm in the rat pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US). By re-presenting the CS during evocation, rats avoid drinking the saccharin. Concomitantly animals display an immunosuppression reflected by an ex vivo reduction in splenic T cell proliferation as well as diminished interleukin-2 and interferon-γ production and cytokine mRNA expression, mimicking the actual effect of the US (CsA). Due to the fact that the kinetics of this behaviorally conditioned immunosuppression are completely unknown, extinction of the conditioned response on the behavioral level (CTA) as well as in the immune response needs to be elucidated together with the neural processes mediating the extinction process. PMID:22791465

  1. Therapy of Lies

    ERIC Educational Resources Information Center

    Price, Sean

    2012-01-01

    Conversion therapy comes in many forms, ranging from informal chats with counselors to aggressive physical coercion, but all are based on the belief that a gay male or a lesbian can be changed "back" to heterosexual behavior. It is not just alarmed parents who turn to this therapy. Many LGBT individuals seek out such treatment in an effort to…

  2. Massage Therapy Research

    ERIC Educational Resources Information Center

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

    2007-01-01

    Massage therapy has been notably effective in preventing prematurity, enhancing growth of infants, increasing attentiveness, decreasing depression and aggression, alleviating motor problems, reducing pain, and enhancing immune function. This review covers massage therapy research from the last decade, as an update to the American Psychologist 1998…

  3. Longitudinal heritability of childhood aggression.

    PubMed

    Porsch, Robert M; Middeldorp, Christel M; Cherny, Stacey S; Krapohl, Eva; van Beijsterveldt, Catharina E M; Loukola, Anu; Korhonen, Tellervo; Pulkkinen, Lea; Corley, Robin; Rhee, Soo; Kaprio, Jaakko; Rose, Richard R; Hewitt, John K; Sham, Pak; Plomin, Robert; Boomsma, Dorret I; Bartels, Meike

    2016-07-01

    The genetic and environmental contributions to the variation and longitudinal stability in childhood aggressive behavior were assessed in two large twin cohorts, the Netherlands Twin Register (NTR), and the Twins Early Development Study (TEDS; United Kingdom). In NTR, maternal ratings on aggression from the Child Behavior Checklist (CBCL) were available for 10,765 twin pairs at age 7, for 8,557 twin pairs at age 9/10, and for 7,176 twin pairs at age 12. In TEDS, parental ratings of conduct disorder from the Strength and Difficulty Questionnaire (SDQ) were available for 6,897 twin pairs at age 7, for 3,028 twin pairs at age 9 and for 5,716 twin pairs at age 12. In both studies, stability and heritability of aggressive behavioral problems was high. Heritability was on average somewhat, but significantly, lower in TEDS (around 60%) than in NTR (between 50% and 80%) and sex differences were slightly larger in the NTR sample. In both studies, the influence of shared environment was similar: in boys shared environment explained around 20% of the variation in aggression across all ages while in girls its influence was absent around age 7 and only came into play at later ages. Longitudinal genetic correlations were the main reason for stability of aggressive behavior. Individual differences in CBCL-Aggressive Behavior and SDQ-Conduct disorder throughout childhood are driven by a comparable but significantly different genetic architecture. © 2016 Wiley Periodicals, Inc. PMID:26786601

  4. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.

    PubMed

    Ren, Guangwen; Zhao, Xin; Zhang, Liying; Zhang, Jimin; L'Huillier, Andrew; Ling, Weifang; Roberts, Arthur I; Le, Anh D; Shi, Songtao; Shao, Changshun; Shi, Yufang

    2010-03-01

    Cell-cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell activation and leukocyte recruitment to the inflammation site and, therefore, plays an important role in evoking effective immune responses. However, we found that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression. When MSCs were cocultured with T cells in the presence of T cell Ag receptor activation, they significantly upregulated the adhesive capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By comparing the immunosuppressive effect of MSCs toward various subtypes of T cells and the expression of these adhesion molecules, we found that the greater expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be inducible by the concomitant presence of IFN-gamma and inflammatory cytokines (TNF-alpha or IL-1). Finally, MSC-mediated immunosuppression was significantly reversed in vitro and in vivo when the adhesion molecules were genetically deleted or functionally blocked, which corroborated the importance of cell-cell contact in immunosuppression by MSCs. Taken together, these findings reveal a novel function of adhesion molecules in immunoregulation by MSCs and provide new insights for the clinical studies of antiadhesion therapies in various immune disorders. PMID:20130212

  5. Combined standard and novel immunosuppressive substances affect B-lymphocyte function.

    PubMed

    Matz, Mareen; Lehnert, Martin; Lorkowski, Christine; Fabritius, Katharina; Weber, Ulrike A; Mashreghi, Mir-Farzin; Neumayer, Hans-H; Budde, Klemens

    2013-04-01

    A considerable fraction of renal transplanted patients is susceptible to humoral rejection. Today well-established therapy regimens are available to control antibody-mediated rejection in the short term. Nevertheless, donor-specific antibodies persist and graft function deteriorates over time. This might be due to insufficient maintenance immunosuppression - which always consists of two to three drugs with different mechanisms of action. Since T- and B-cell functions always depend on each other in the alloimmune response it is of interest to analyze the effects of combined standard and new immunosuppressive substances with T-cell inhibitory properties on B-cell function. The effectiveness of complementary administrations of sotrastaurin, mycophenolic acid and everolimus on the activation and function of human primary B-lymphocytes was tested. Everolimus and mycophenolic acid alone and in combination proved to be highly effective in suppressing B-cell activation, whereas the proteinkinase C inhibitor sotrastaurin had an unexpected and reverse impact on various B-cell functions when applied in combination with the mammalian target of rapamycin and the inosine monophosphate dehydrogenase inhibitor. PMID:23499640

  6. Intensive Pharmacological Immunosuppression Allows for Repetitive Liver Gene Transfer With Recombinant Adenovirus in Nonhuman Primates

    PubMed Central

    Fontanellas, Antonio; Hervás-Stubbs, Sandra; Mauleón, Itsaso; Dubrot, Juan; Mancheño, Uxua; Collantes, María; Sampedro, Ana; Unzu, Carmen; Alfaro, Carlos; Palazón, Asis; Smerdou, Cristian; Benito, Alberto; Prieto, Jesús; Peñuelas, Iván; Melero, Ignacio

    2010-01-01

    Repeated administration of gene therapies is hampered by host immunity toward vectors and transgenes. Attempts to circumvent antivector immunity include pharmacological immunosuppression or alternating different vectors and vector serotypes with the same transgene. Our studies show that B-cell depletion with anti-CD20 monoclonal antibody and concomitant T-cell inhibition with clinically available drugs permits repeated liver gene transfer to a limited number of nonhuman primates with recombinant adenovirus. Adenoviral vector–mediated transfer of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene was visualized in vivo with a semiquantitative transgene-specific positron emission tomography (PET) technique, liver immunohistochemistry, and immunoblot for the reporter transgene in needle biopsies. Neutralizing antibody and T cell–mediated responses toward the viral capsids were sequentially monitored and found to be repressed by the drug combinations tested. Repeated liver transfer of the HSV1-tk reporter gene with the same recombinant adenoviral vector was achieved in macaques undergoing a clinically feasible immunosuppressive treatment that ablated humoral and cellular immune responses. This strategy allows measurable gene retransfer to the liver as late as 15 months following the first adenoviral exposure in a macaque, which has undergone a total of four treatments with the same adenoviral vector. PMID:20087317

  7. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care.

    PubMed

    Gentile, Lori F; Cuenca, Alex G; Efron, Philip A; Ang, Darwin; Bihorac, Azra; McKinley, Bruce A; Moldawer, Lyle L; Moore, Frederick A

    2012-06-01

    Surgical intensive care unit (ICU) stay of longer than 10 days is often described by the experienced intensivist as a "complicated clinical course" and is frequently attributed to persistent immune dysfunction. "Systemic inflammatory response syndrome" (SIRS) followed by "compensatory anti-inflammatory response syndrome" (CARS) is a conceptual framework to explain the immunologic trajectory that ICU patients with severe sepsis, trauma, or emergency surgery for abdominal infection often traverse, but the causes, mechanisms, and reasons for persistent immune dysfunction remain unexplained. Often involving multiple-organ failure (MOF) and death, improvements in surgical intensive care have altered its incidence, phenotype, and frequency and have increased the number of patients who survive initial sepsis or surgical events and progress to a persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Often observed, but rarely reversible, these patients may survive to transfer to a long-term care facility only to return to the ICU, but rarely to self-sufficiency. We propose that PICS is the dominant pathophysiology and phenotype that has replaced late MOF and prolongs surgical ICU stay, usually with poor outcome. This review details the evolving epidemiology of MOF, the clinical presentation of PICS, and our understanding of how persistent inflammation and immunosuppression define the pathobiology of prolonged intensive care. Therapy for PICS will involve innovative interventions for immune system rebalance and nutritional support to regain physical function and well-being. PMID:22695412

  8. Successful Immunosuppressive Treatment of Mixed Connective Tissue Disease Complicated by Microscopic Polyangiitis.

    PubMed

    Sato, Shuzo; Yashiro, Makiko; Matsuoka, Naoki; Uematsu, Manabu; Asano, Tomoyuki; Kobayashi, Hiroko; Watanabe, Hiroshi; Ohira, Hiromasa

    2016-01-01

    Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with elevated antibodies to U1 small nuclear ribonucleoprotein (U1-RNP). MCTD is often accompanied by interstitial lung disease as pulmonary involvement. On the other hand, microscopic polyangiitis (MPA) is a systemic autoimmune disease characterized by the inflammation of small vessels (arterioles, capillaries, and venules) mainly affecting the lung and kidney. MPA is associated with elevated serum anti-neutrophil cytoplasmic antibody (ANCA). Complication of MPA in patients with MCTD is rare. So far, only nine case reports of MCTD complicated by MPA with serum myeloperoxidase-specific ANCA (MPO-ANCA) are available. Here, we describe a 64-year-old male suffering from MCTD with MPA. The patient developed interstitial pneumonia with alveolar hemorrhage accompanied by myositis, scleroderma, and elevated anti-U1-RNP antibody and MPO-ANCA levels with substantial systemic inflammation. Strong immunosuppressive therapy (corticosteroid, intravenous immunoglobulin, and cyclosporine A) ameliorated the myositis, interstitial lung disease, and inflammation, with the decrease of MPO-ANCA levels, despite that severe lung complications are often associated with poor outcomes. In conclusion, MCTD may be accompanied by MPA with alveolar hemorrhage. Severe lung complications may indicate a poor outcome, and therefore prompt immunosuppressive treatment should be performed in such patients. PMID:27238624

  9. Transient immunosuppression: a bridge between infection and the atypical autoimmunity of Guillain–Barré syndrome?

    PubMed Central

    Steiner, I; Rosenberg, G; Wirguin, I

    2010-01-01

    Guillain–Barré syndrome (GBS) is an acute, usually monophasic, disorder of the peripheral nervous system that is assumed to be of immune-mediated pathogenesis. However, several clinical features and experimental findings of GBS are uncharacteristic for an immune-mediated disorder and set this condition apart from other disorders with a putative immune-mediated pathogenesis. These features include, among others, the monophasic nature of GBS, the lack of response to immunosuppressive (unlike immunomodulatory) therapy, the absence of a typical association with immunogenetic background and the inability to establish a valid and relevant animal model. We suggest a comprehensive hypothesis for the pathogenesis of GBS that is based on the assumption that the condition is due to a transient (or occasionally chronic) immune deficiency, as in most cases GBS follows an infection with pathogens known to induce immunosuppression. Such infections may be followed by breakdown of immune tolerance and induction of an immune attack on peripheral nerves. Mounting of the immune-mediated assault might be triggered either by the same infective pathogen or by secondary infection. Clearance of the infection and resumption of a normal immune response and tolerance eventually terminate the immune-mediated damage to the peripheral nerves and enable recovery. This hypothesis assumes that the entire sequence of events that culminates in GBS is due to transient exogenous factors and excludes a significant role for inherent host susceptibility, which explains the monophasic nature of the disorder. PMID:20735441

  10. Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy.

    PubMed

    Kabat-Koperska, J; Kolasa-Wołosiuk, A; Wojciuk, B; Wojciechowska-Koszko, I; Roszkowska, P; Krasnodębska-Szponder, B; Paczkowska, E; Safranow, K; Gołembiewska, E; Machaliński, B; Ciechanowski, K

    2016-06-01

    This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner. PMID:27007325

  11. Normative beliefs about aggression and cyber aggression among young adults: a longitudinal investigation.

    PubMed

    Wright, Michelle F; Li, Yan

    2013-01-01

    This longitudinal study examined normative beliefs about aggression (e.g., face-to-face, cyber) in relation to the engagement in cyber aggression 6 months later among 126 (69 women) young adults. Participants completed electronically administered measures assessing their normative beliefs, face-to-face and cyber aggression at Time 1, and cyber aggression 6 months later (Time 2). We found that men reported more cyber relational and verbal aggression when compared to women. After controlling for each other, Time 1 face-to-face relational aggression was positively related to Time 2 cyber relational aggression, whereas Time 1 face-to-face verbal aggression was positively related to Time 2 cyber verbal aggression. Normative beliefs regarding cyber aggression was positively related to both forms of cyber aggression 6 months later, after controlling for normative beliefs about face-to-face aggression. Furthermore, a significant two-way interaction between Time 1 cyber relational aggression and normative beliefs about cyber relational aggression was found. Follow-up analysis showed that Time 1 cyber relational aggression was more strongly related to Time 2 cyber relational aggression when young adults held higher normative beliefs about cyber relational aggression. A similar two-way interaction was found for cyber verbal aggression such that the association between Time 1 and Time 2 cyber verbal aggression was stronger at higher levels of normative beliefs about cyber verbal aggression. Results are discussed in terms of the social cognitive and behavioral mechanisms associated with the engagement of cyber aggression. PMID:23440595

  12. Aggressive multiple sclerosis: proposed definition and treatment algorithm.

    PubMed

    Rush, Carolina A; MacLean, Heather J; Freedman, Mark S

    2015-07-01

    Multiple sclerosis (MS) is a CNS disorder characterized by inflammation, demyelination and neurodegeneration, and is the most common cause of acquired nontraumatic neurological disability in young adults. The course of the disease varies between individuals: some patients accumulate minimal disability over their lives, whereas others experience a rapidly disabling disease course. This latter subset of patients, whose MS is marked by the rampant progression of disability over a short time period, is often referred to as having 'aggressive' MS. Treatment of patients with aggressive MS is challenging, and optimal strategies have yet to be defined. It is important to identify patients who are at risk of aggressive MS as early as possible and implement an effective treatment strategy. Early intervention might protect patients from irreversible damage and disability, and prevent the development of a secondary progressive course, which thus far lacks effective therapy. PMID:26032396

  13. Adolescents' Social Reasoning about Relational Aggression

    ERIC Educational Resources Information Center

    Goldstein, Sara E.; Tisak, Marie S.

    2010-01-01

    We examined early adolescents' reasoning about relational aggression, and the links that their reasoning has to their own relationally aggressive behavior. Thinking about relational aggression was compared to thinking about physical aggression, conventional violations, and personal behavior. In individual interviews, adolescents (N = 103) rated…

  14. The Development of Aggression within Sibling Conflict.

    ERIC Educational Resources Information Center

    Martin, Jacqueline L.; Ross, Hildy S.

    1995-01-01

    A longitudinal study examined responses to physically aggressive conflicts among siblings. Found that parents respond to half of children's aggression (especially if there is crying). Most parent and child responses were simple commands to stop the aggression. Reasoning was used less often, and physical intervention, rarely. Aggression was higher…

  15. Do Teachers Misbehave? Aggression in School Teams

    ERIC Educational Resources Information Center

    Ben Sasson, Dvora; Somech, Anit

    2015-01-01

    Purpose: Despite growing research on school aggression, significant gaps remain in the authors' knowledge of team aggression, since most studies have mainly explored aggression on the part of students. The purpose of this paper is to focus on understanding the phenomenon of workplace aggression in school teams. Specifically, the purpose of the…

  16. Attributional bias and reactive aggression.

    PubMed

    Hudley, C; Friday, J

    1996-01-01

    This article looks at a cognitive behavioral intervention designed to reduce minority youths' (Latino and African-American boys) levels of reactive peer-directed aggression. The BrainPower Program trains aggressive boys to recognize accidental causation in ambiguous interactions with peers. The objective of this research is to evaluate the effectiveness of this attribution retraining program in reducing levels of reactive, peer-directed aggression. This research hypothesizes that aggressive young boys' tendency to attribute hostile intentions to others in ambiguous social interactions causes display of inappropriate, peer-directed aggression. A reduction in attributional bias should produce a decrease in reactive physical and verbal aggression directed toward peers. A 12-session, attributional intervention has been designed to reduce aggressive students' tendency to infer hostile intentions in peers following ambiguous peer provocations. The program trains boys to (1) accurately perceive and categorize the available social cues in interactions with peers, (2) attribute negative outcomes of ambiguous causality to accidental or uncontrollable causes, and (3) generate behaviors appropriate to these retrained attributions. African-American and Latino male elementary-school students (N = 384), in grades four-six, served as subjects in one of three groups: experimental attribution retraining program, attention training, and no-attention control group. Three broad categories of outcome data were collected: teacher and administrator reports of behavior, independent observations of behavior, and self-reports from participating students. Process measures to assess implementation fidelity include videotaped training sessions, observations of intervention sessions, student attendance records, and weekly team meetings. The baseline data indicated that students who were evenly distributed across the four sites were not significantly different on the baseline indicators: student

  17. Kindergarten Children's Genetic Vulnerabilities Interact with Friends' Aggression to Promote Children's Own Aggression

    ERIC Educational Resources Information Center

    van Lier, Pol; Boivin, Michel; Dionne, Ginette; Vitaro, Frank; Brendgen, Mara; Koot, Hans; Tremblay, Richard E.; Perusse, Daniel

    2007-01-01

    Objective: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors. Method: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as teacher and peer reports of aggression of the two best…

  18. [Treatment of inter-specific aggression in cats with the selective serotonin reuptake inhibitor fluvoxamine. A case report].

    PubMed

    Sprauer, S

    2012-01-01

    The article describes the redirected, inter-specific aggression of a Maine Coon cat, which was principally directed towards the owners. The cat reacted towards different, nonspecific sounds with abrupt aggressive behaviour and injured the victims at this juncture with moderate scratching and biting. Exclusively using behaviour therapy did not achieve the desired result, thus the therapy was supported with pharmaceuticals. The cat orally received the selective serotonin re-uptake inhibitor fluvoxamine at an initial dosage of 0.5mg/kg BW once daily. After 4 weeks the application rate was increased to 1.0 mg/kg BW once daily. The medication did not cause any side effects. Together with the behaviour-modulating therapy, carried out parallel to the medication therapy, the aggressive behaviour problem of the cat was resolved. After administration for a period of 63 weeks the fluvoxamine therapy was discontinued by gradually reducing the dose without recurrence of the aggressive behaviour. PMID:23242225

  19. In silico tumor control induced via alternating immunostimulating and immunosuppressive phases

    PubMed Central

    Reppas, AI; Alfonso, JCL; Hatzikirou, H

    2016-01-01

    Despite recent advances in the field of Oncoimmunology, the success potential of immunomodulatory therapies against cancer remains to be elucidated. One of the reasons is the lack of understanding on the complex interplay between tumor growth dynamics and the associated immune system responses. Toward this goal, we consider a mathematical model of vascularized tumor growth and the corresponding effector cell recruitment dynamics. Bifurcation analysis allows for the exploration of model's dynamic behavior and the determination of these parameter regimes that result in immune-mediated tumor control. In this work, we focus on a particular tumor evasion regime that involves tumor and effector cell concentration oscillations of slowly increasing and decreasing amplitude, respectively. Considering a temporal multiscale analysis, we derive an analytically tractable mapping of model solutions onto a weakly negatively damped harmonic oscillator. Based on our analysis, we propose a theory-driven intervention strategy involving immunostimulating and immunosuppressive phases to induce long-term tumor control. PMID:26305801

  20. Biomarkers of aggression in dementia.

    PubMed

    Gotovac, Kristina; Nikolac Perković, Matea; Pivac, Nela; Borovečki, Fran

    2016-08-01

    Dementia is a clinical syndrome defined by progressive global impairment of acquired cognitive abilities. It can be caused by a number of underlying conditions. The most common types of dementia are Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular cognitive impairment (VCI) and dementia with Lewy bodies (DLB). Despite the fact that cognitive impairment is central to the dementia, noncognitive symptoms, most commonly described nowadays as neuropsychiatric symptoms (NPS) exist almost always at certain point of the illness. Aggression as one of the NPS represents danger both for patients and caregivers and the rate of aggression correlates with the loss of independence, cognitive decline and poor outcome. Therefore, biomarkers of aggression in dementia patients would be of a great importance. Studies have shown that different genetic factors, including monoamine signaling and processing, can be associated with various NPS including aggression. There have been significant and multiple neurotransmitter changes identified in the brains of patients with dementia and some of these changes have been involved in the etiology of NPS. Aggression specific changes have also been observed in neuropathological studies. The current consensus is that the best approach for development of such biomarkers may be incorporation of genetics (polymorphisms), neurobiology (neurotransmitters and neuropathology) and neuroimaging techniques. PMID:26952705

  1. Why are small males aggressive?

    PubMed Central

    Morrell, Lesley J; Lindström, Jan; Ruxton, Graeme D

    2005-01-01

    Aggression is ubiquitous in the animal kingdom, whenever the interests of individuals conflict. In contests between animals, the larger opponent is often victorious. However, counter intuitively, an individual that has little chance of winning (generally smaller individuals) sometimes initiates contests. A number of hypotheses have been put forward to explain this behaviour, including the ‘desperado effect’ according to which, the likely losers initiate aggression due to lack of alternative options. An alternative explanation suggested recently is that likely losers attack due to an error in perception: they mistakenly perceive their chances of winning as being greater than they are. We show that explaining the apparently maladaptive aggression initiated by the likely loser can be explained on purely economic grounds, without requiring either the desperado effect or perception errors. Using a game-theoretical model, we show that if smaller individuals can accurately assess their chance of winning, if this chance is less than, but close to, a half, and if resources are scarce (or the contested resource is of relatively low value), they are predicted to be as aggressive as their larger opponents. In addition, when resources are abundant, and small individuals have some chance of winning, they may be more aggressive than their larger opponents, as it may benefit larger individuals to avoid the costs of fighting and seek alternative uncontested resources. PMID:16024387

  2. Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection.

    PubMed

    Peppa, Dimitra; Micco, Lorenzo; Javaid, Alia; Kennedy, Patrick T F; Schurich, Anna; Dunn, Claire; Pallant, Celeste; Ellis, Gidon; Khanna, Pooja; Dusheiko, Geoffrey; Gilson, Richard J; Maini, Mala K

    2010-01-01

    NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing them to kill hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to 31 healthy controls. We found that, in contrast to their upregulated TRAIL expression and maintenance of cytolytic function, NK cells had a markedly impaired capacity to produce IFN-γ in CHB. This functional dichotomy of NK cells could be recapitulated in vitro by exposure to the immunosuppressive cytokine IL-10, which was induced in patients with active CHB. IL-10 selectively suppressed NK cell IFN-γ production without altering cytotoxicity or death ligand expression. Potent antiviral therapy reduced TRAIL-expressing CD56(bright) NK cells, consistent with the reduction in liver inflammation it induced; however, it was not able to normalise IL-10 levels or the capacity of NK cells to produce the antiviral cytokine IFN-γ. Blockade of IL-10 +/- TGF-β restored the capacity of NK cells from both the periphery and liver of patients with CHB to produce IFN-γ, thereby enhancing their non-cytolytic antiviral capacity. In conclusion, NK cells may be driven to a state of partial functional tolerance by the immunosuppressive cytokine environment in CHB. Their defective capacity to produce the antiviral cytokine IFN-γ persists in patients on antiviral therapy but can be corrected in vitro by IL-10+/- TGF-β blockade. PMID:21187913

  3. Pneumocystis jiroveci pneumonia in patients treated with systemic immunosuppressive agents for dermatologic conditions: a systematic review with recommendations for prophylaxis.

    PubMed

    Gonzalez Santiago, Tania M; Wetter, David A; Kalaaji, Amer N; Limper, Andrew H; Lehman, Julia S

    2016-08-01

    Pneumocystis jiroveci pneumonia is an opportunistic infection associated with substantial rates of mortality in immunosuppressed patients. Prophylaxis recommendations are mostly targeted toward patients with non-dermatologic diagnoses. This study was conducted to determine when dermatology patients treated with immunosuppressive medications should be offered P. jiroveci pneumonia prophylaxis. We searched the literature from January 1, 1993, to December 31, 2013, using terms relating to P. jiroveci pneumonia and dermatologic diagnoses to analyze the clinical characteristics of previously affected patients. Guidelines for P. jiroveci pneumonia prophylaxis from other medical fields were also analyzed. Of 17 dermatology patients reported to have contracted P. jiroveci pneumonia, eight (47.1%) died of the pneumonia. Risk factors included lack of prophylaxis, systemic corticosteroid therapy, lymphopenia, hypoalbuminemia, low serum CD4 counts, comorbid pulmonary or renal disease, malignancy, and prior organ transplantation. The present conclusions are limited by heterogeneity among the selected studies and limitations in their identification and selection. However, P. jiroveci pneumonia in dermatology patients is associated with a high mortality rate. Based on our analysis, we propose that prophylaxis be considered in dermatology patients in whom treatment with systemic corticosteroids at doses exceeding 20 mg/day or treatment with corticosteroid-sparing immunosuppressive agents is anticipated for at least 4 weeks, and in patients with additional risk factors for P. jiroveci pneumonia. PMID:27009930

  4. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats

    PubMed Central

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Wojciuk, Bartosz; Wojciechowska-Koszko, Iwona; Roszkowska, Paulina; Krasnodębska-Szponder, Barbara; Paczkowska, Edyta; Safranow, Krzysztof; Gołembiewska, Edyta; Machaliński, Bogusław; Ciechanowski, Kazimierz

    2016-01-01

    Background In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system – the thymus and the spleen. Methods The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Conclusion Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen–dependent manner. PMID:27471376

  5. Accuracy in Judgments of Aggressiveness

    PubMed Central

    Kenny, David A.; West, Tessa V.; Cillessen, Antonius H. N.; Coie, John D.; Dodge, Kenneth A.; Hubbard, Julie A.; Schwartz, David

    2009-01-01

    Perceivers are both accurate and biased in their understanding of others. Past research has distinguished between three types of accuracy: generalized accuracy, a perceiver’s accuracy about how a target interacts with others in general; perceiver accuracy, a perceiver’s view of others corresponding with how the perceiver is treated by others in general; and dyadic accuracy, a perceiver’s accuracy about a target when interacting with that target. Researchers have proposed that there should be more dyadic than other forms of accuracy among well-acquainted individuals because of the pragmatic utility of forecasting the behavior of interaction partners. We examined behavioral aggression among well-acquainted peers. A total of 116 9-year-old boys rated how aggressive their classmates were toward other classmates. Subsequently, 11 groups of 6 boys each interacted in play groups, during which observations of aggression were made. Analyses indicated strong generalized accuracy yet little dyadic and perceiver accuracy. PMID:17575243

  6. Forging a link between oncogenic signaling and immunosuppression in melanoma.

    PubMed

    Khalili, Jahan S; Hwu, Patrick; Lizée, Gregory

    2013-02-01

    Immunosuppressive tumor microenvironments limit the efficacy of T cell-based immunotherapy. We have recently demonstrated that the inhibition of BRAF(V600E) with vemurafenib relieves interleukin-1 (IL-1)-induced T-cell suppression as mediated by melanoma tumor associated fibroblasts (TAFs). These results suggest that inhibitors of the MAPK pathway in combination with T cell-based immunotherapies may induce long-lasting and durable responses. PMID:23525189

  7. A case for varicella vaccination in the immunosuppressed

    PubMed Central

    Holmes, Michael Vaclav; Atabani, Sowsan F; Khan, Nasser; Steiner, Kate; Haque, Tanzina; Slapak, Gabrielle

    2009-01-01

    A middle-aged man with long-standing Crohn disease maintained in remission on low-dose immunosuppression presented with abdominal pain. Over the following few days he developed a vesicular rash, became dyspnoeic, confused and had two seizures. Despite high-dose intravenous aciclovir, he died. Disseminated varicella zoster virus, the cause of his death, could potentially have been prevented had he received varicella vaccination at an earlier stage. PMID:21686799

  8. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    SciTech Connect

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-05-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.

  9. Methylenedioxymethamphetamine ('Ecstasy')-induced immunosuppression: a cause for concern?

    PubMed

    Boyle, Noreen T; Connor, Thomas J

    2010-09-01

    Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a ring-substituted amphetamine and a popular drug of abuse. In addition to ability to induce euphoria, MDMA abuse is associated with a range of acute and long-term hazardous effects. This paper is focused on once such adverse effect: its ability to negatively impact on functioning of the immune system. Research demonstrates that MDMA has immunosuppressive properties, with both innate and adaptive arms of the immune system being affected. The ability of MDMA to suppress innate immunity is indicated by impaired neutrophil phagocytosis and reduced production of dendritic cell/macrophage-derived pro-inflammatory cytokines including tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-12 and IL-15. MDMA also suppresses innate IFN-gamma production, and considering the role of IFN-gamma in priming antigen-presenting cells, it is not surprising that MDMA reduces MHC class II expression on dendritic cells and macrophages, and inhibits co-stimulatory molecule expression. Paradoxically, studies demonstrate that MDMA elicits pro-inflammatory actions in the CNS by activating microglia, the resident innate immune cells in the brain. In terms of adaptive immunity, MDMA reduces circulating lymphocyte numbers, particularly CD4(+) T-cells; suppresses T-cell proliferation; and skews cytokine production in a Th(2) direction. For the most part, the immunosuppressive effects of MDMA cannot be attributed to a direct action of the drug on immune cells, but rather due to the release of endogenous immunomodulatory substances. In this regard, peripheral beta-adrenoceptors and cholinergic receptors have been shown to mediate some immunosuppressive effects of MDMA. Finally, we discuss emerging evidence indicating that MDMA-induced immunosuppression can translate into significant health risks for abusers. PMID:20718737

  10. Immunosuppression Decreases Inflammation and Increases AAV6-hSERCA2a-Mediated SERCA2a Expression

    PubMed Central

    Zhu, Xiaodong; McTiernan, Charles F.; Rajagopalan, Navin; Shah, Hemal; Fischer, David; Toyoda, Yoshiya; Letts, Dustin; Bortinger, Jonathan; Gibson, Gregory; Xiang, Wenyu; McCurry, Kenneth; Mathier, Michael; Glorioso, Joseph C.

    2012-01-01

    Abstract The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF). Increasing SERCA2a expression in HF models improves cardiac function. We used direct cardiac delivery of adeno-associated virus encoding human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety, efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were analyzed for hSERCA2a expression (Western blot) and immune responses (histology and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks and then declined (to ∼50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05) whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a developed neutralizing antibodies (titer ≥1:120) and cardiac cellular infiltration. Immunosuppression dramatically reduced immune responses (reduced inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a expression and improves cardiac function. However, the hSERCA2a protein level is reduced by host immune responses. Immunosuppression alleviates immune responses and sustains transgene expression, and may be an important adjuvant for clinical gene therapy trials. PMID:22482463

  11. Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers.

    PubMed

    Oswald, S; Nassif, A; Modess, C; Keiser, M; Hanke, U; Engel, A; Lütjohann, D; Weitschies, W; Siegmund, W

    2010-06-01

    Organ transplant recipients who have dyslipidemia related to immunosuppression may benefit from cholesterol-lowering therapy with ezetimibe, a substrate of ABCB1, ABCC2, and OATP1B1. Adverse pharmacokinetic interactions are hypothesized with sirolimus, which is a substrate of OATP1B1 and OATP1B3 and an inhibitor of ABCB1, OATP1B1, and OATP1B3 but not of ABCC2. However, competition between sirolimus and ezetimibe for ABCB1 and OATP1B1 is not of major clinical relevance, as confirmed in our randomized, controlled, single-dose study in healthy subjects. PMID:20220747

  12. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment.

    PubMed

    Axelrad, Jordan E; Lichtiger, Simon; Yajnik, Vijay

    2016-05-28

    In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes. PMID:27239106

  13. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus–Seropositive Patients

    PubMed Central

    Kittleson, Michelle M.; Dilibero, Deanna; Hardy, W. David; Kobashigawa, Jon A.; Esmailian, Fardad

    2016-01-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus—accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation. PMID:27047290

  14. Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment

    PubMed Central

    Axelrad, Jordan E; Lichtiger, Simon; Yajnik, Vijay

    2016-01-01

    In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes. PMID:27239106

  15. Nonsurgical treatment of aggressive fibromatosis in the head and neck

    SciTech Connect

    West, C.B. Jr.; Shagets, F.W.; Mansfield, M.J. )

    1989-09-01

    Aggressive fibromatosis is a poorly defined, locally aggressive, yet histologically benign fibroblastic proliferative lesion that may occur in the head and neck. The lesion is highly cellular and locally infiltrative and has a propensity to invade and erode bone, compromising vital structures within the head and neck. However, it is not a true malignancy because it does not have malignant cytologic characteristics nor does it metastasize. We present two cases of aggressive fibromatosis occurring in young adult men. The first case involved a rapidly enlarging mass of the anterior maxilla that involved the upper lip, nasal alae, nasal septum, inferior turbinates, and hard palate. The patient underwent incisional biopsy to confirm the diagnosis. Because of difficulty in determining the actual margins of this extensive lesion and the significant morbidity that would have resulted from surgical resection, we elected to treat this patient with chemotherapy and radiation therapy. The second case was an extensive lesion involving the right temporal bone, pterygomaxillary space, and infratemporal, temporal, and middle cranial fossae. Incisional biopsy confirmed the diagnosis. Because of the lack of functional and cosmetic deficits and the unavoidable morbidity of a surgical resection, this patient was treated with radiation therapy. Although wide field resection is the most satisfactory form of treatment, in situations in which this modality would result in unacceptable morbidity or if surgical margins are positive, then radiation therapy and chemotherapy should be considered. Support for these therapeutic modalities is found in larger series of cases outside the head and neck.

  16. Teachers' Reactions to Children's Aggression

    ERIC Educational Resources Information Center

    Nesdale, Drew; Pickering, Kaye

    2006-01-01

    Drawing on social schema theory (Fiske & Taylor, 1991) and social identity theory (Tajfel & Turner, 1979), this study examined the impact on teachers' reactions to children's aggression of three variables, two of which were related to the aggressors and one was related to the teachers. Experienced female elementary school teachers (N=90) each read…

  17. Explorations of Affection and Aggression.

    ERIC Educational Resources Information Center

    Shuntich, Richard J.; Shapiro, Richard

    Considerable effort has been devoted to investigating various aspects of love and affection, but there have been few studies about direct expressions of affection. Relationships between gender composition of a dyad and the affection/aggression expressed by the dyad were examined as was the possibility of increasing the amount of affectionate…

  18. Risperidone and Explosive Aggressive Autism.

    ERIC Educational Resources Information Center

    Horrigan, Joseph P.; Barnhill, L. Jarrett

    1997-01-01

    In this study, 11 males with autism and mental retardation were administered risperidone. Substantial clinical improvement was noted almost immediately; patients with aggression, self-injury, explosivity, and poor sleep hygiene were most improved. The modal dose for optimal response was 0.5 mg bid. Weight gain was a significant side effect.…

  19. Male Responses to Female Aggression.

    ERIC Educational Resources Information Center

    Russell, Gordon W.; And Others

    1988-01-01

    Randomly assigned 60 male undergraduates to view film clip of professional lady wrestlers or of mud wrestling, or to no-film control. Both films produced negative changes in mood states, principally increase in aggression and decrease in social affection. Viewing films did not produce changes in men's acceptance of interpersonal violence against…

  20. The Passive Aggressive Conflict Cycle

    ERIC Educational Resources Information Center

    Whitson, Signe

    2013-01-01

    Understanding the Passive Aggressive Conflict Cycle (PACC) helps observers to be able to look beyond behavior and better understand what is occurring beneath the surface. This article presents a real-life example of a seemingly minor conflict between a teacher and child that elicited an apparent major overreaction by the adult. Also provided is a…

  1. Television Portrayal and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Comstock, George

    This is a review of research relating to the attributes of portrayals which play a role in affecting aggressive behavior. The effects of portrayal can occur at any of three successive stages: acquisition, disinhibition/stimulation/arousal, performance. The older the individual, the more likely the influence is to be in all three stages of…

  2. Biochemistry and Aggression: Psychohematological Model.

    ERIC Educational Resources Information Center

    Foster, Hilliard G., Jr.; Spitz, Reuben T.

    1994-01-01

    Examines biochemical measures in a population of forensic psychiatric inpatients. Regression equations utilizing chemical and biological variables were developed and evaluated to determine their value in predicting the severity and frequency of aggression. Findings strongly suggest the presence of specific biochemical alteration among those…

  3. Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells.

    PubMed

    Wen, Amy M; Lee, Karin L; Cao, Pengfei; Pangilinan, Katrina; Carpenter, Bradley L; Lam, Patricia; Veliz, Frank A; Ghiladi, Reza A; Advincula, Rigoberto C; Steinmetz, Nicole F

    2016-05-18

    Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment. PMID:27077475

  4. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    SciTech Connect

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-02-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced.

  5. Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.

    PubMed

    Cameron, A M; Wesson, R N; Ahmadi, A R; Singer, A L; Hu, X; Okabayashi, T; Wang, Y; Shigoka, M; Fu, Y; Gao, W; Raccusen, L C; Montgomery, R A; Williams, G M; Sun, Z

    2016-07-01

    Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years. PMID:26748958

  6. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men.

    PubMed

    O'Connor, Daryl B; Archer, John; Hair, W Morton; Wu, Frederick C W

    2002-04-01

    To investigate (1) the effects of exogenous testosterone (T) on self- and partner-reported aggression and mood and (2) the role of trait impulsivity in the T-aggression relationship. Thirty eugonadal men with partners were randomized into two treatment groups to receive: (1) 200 mg im T enanthate weekly for 8 weeks or (2) 200 mg im sodium chloride weekly for 8 weeks. Eight hypogonadal men received 200 mg im T enanthate biweekly for 8 weeks. All groups completed a battery of behavior measures at baseline (Week 0) and at Weeks 4 and 8. Cognitive and motor impulsivity were the only predictors of self-reported total aggression (over and above age and T levels) at Weeks 0, 4, and 8. No significant changes in aggression or mood levels were found in the eugonadal-treated group. Significant reductions in negative mood (tension, anger, and fatigue) followed by an increase in vigor were found in response to T treatment in the hypogonadal group. These results demonstrate that inability to control one's behavior when such control is required by a particular situation (impulsivity) was found to significantly predict levels of aggression over and above age and T level. These data do not support the hypothesis that supraphysiological levels of T (within this range) lead to an increase in self- and partner-reported aggression or mood disturbances. Instead, for the first time, this study has identified the high level of negative affect experienced by hypogonadal patients. These findings have implications for T replacement therapy and male contraception. PMID:12062320

  7. Implicit cognitive aggression among young male prisoners: Association with dispositional and current aggression.

    PubMed

    Ireland, Jane L; Adams, Christine

    2015-01-01

    The current study explores associations between implicit and explicit aggression in young adult male prisoners, seeking to apply the Reflection-Impulsive Model and indicate parity with elements of the General Aggression Model and social cognition. Implicit cognitive aggressive processing is not an area that has been examined among prisoners. Two hundred and sixty two prisoners completed an implicit cognitive aggression measure (Puzzle Test) and explicit aggression measures, covering current behaviour (DIPC-R) and aggression disposition (AQ). It was predicted that dispositional aggression would be predicted by implicit cognitive aggression, and that implicit cognitive aggression would predict current engagement in aggressive behaviour. It was also predicted that more impulsive implicit cognitive processing would associate with aggressive behaviour whereas cognitively effortful implicit cognitive processing would not. Implicit aggressive cognitive processing was associated with increased dispositional aggression but not current reports of aggressive behaviour. Impulsive implicit cognitive processing of an aggressive nature predicted increased dispositional aggression whereas more cognitively effortful implicit cognitive aggression did not. The article concludes by outlining the importance of accounting for implicit cognitive processing among prisoners and the need to separate such processing into facets (i.e. impulsive vs. cognitively effortful). Implications for future research and practice in this novel area of study are indicated. PMID:25857854

  8. Overview of biological therapy in ulcerative colitis: current and future directions.

    PubMed

    Furfaro, Federica; Bezzio, Cristina; Ardizzone, Sandro; Massari, Alessandro; de Franchis, Roberto; Maconi, Giovanni

    2015-06-01

    The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly. To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies. The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse. PMID:26114181

  9. Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma

    PubMed Central

    Miller, Natalie J.; Bhatia, Shailender; Parvathaneni, Upendra; Iyer, Jayasri G.; Nghiem, Paul

    2013-01-01

    Opinion statement Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a disease-specific mortality of approximately 40 %. The association of MCC with a recently discovered polyomavirus, combined with the increased incidence and mortality of MCC among immunocompromised patients, highlight the importance of the immune system in controlling this cancer. Initial management of MCC is summarized within the NCCN guidelines and in recently published reviews. The high rate of recurrent and metastatic disease progression in MCC, however, presents a major challenge in a cancer that lacks mechanism-based, disease-specific therapies. Traditional treatment approaches have focused on cytotoxic chemotherapy that, despite frequent initial efficacy, rarely provides durable responses and has high morbidity among the elderly. In addition, the immunosuppressive nature of chemotherapy is of concern when treating a virus-associated cancer for which survival is unusually tightly linked to immune function. With a median survival of 9.6 months after development of an initial metastasis (n=179, described herein), and no FDA-approved agents for this cancer, there is an urgent need for more effective treatments. We review diverse management options for patients with advanced MCC, with a focus on emerging and mechanism-based therapies, some of which specifically target persistently expressed viral antigens. These treatments include single-dose radiation and novel immunotherapies, some of which are in clinical trials. Due to their encouraging efficacy, low toxicity, and lack of immune suppression, these therapies may offer viable alternatives to traditional cytotoxic chemotherapy. PMID:23436166

  10. [Rapidly evolving diabetic mononeuritis multiplex. Favorable outcome after immunosuppressive treatment].

    PubMed

    Awada, A; Dehoux, E; al Jumah, M; al Ayafi, H

    2001-11-01

    A 61 year-old man with type 2 diabetes mellitus presented with an extremely rapid and aggressive mononeuritis multiplex. Four months after onset, he had severe postural hypotension and at least 6 cranial nerves and 4 somatic nerves were involved. Extensive work-up failed to discover any etiology for the neuropathy apart from diabetes. Treatment with corticosteroids, i.v. immunoglobulins and cyclosporin was followed by progressive but sustained improvement. This case and few other published ones suggest that some particularly aggressive forms of diabetic neuropathy have an immune mechanism and may be treated favorably with immunosuppressor drugs. PMID:11924012

  11. A Psychoeducational Group for Aggressive Adolescent Girls

    ERIC Educational Resources Information Center

    Cummings, Anne L.; Hoffman, Sue; Leschied, Alan W.

    2004-01-01

    This article describes an eight-session psychoeducational group for aggressive adolescent girls. The content of the group sessions is based on research that has identified gender-specific issues related to aggression in adolescent girls, such as gender-role socialization, childhood abuse, relational aggression, horizontal violence, and girl…

  12. Aggressive behavior in children and adolescents.

    PubMed

    Zahrt, Dawn M; Melzer-Lange, Marlene D

    2011-08-01

    After completing this article, readers should be able to: 1. Describe the developmental stages of aggressive behavior in children.2. Know how to provide parents with support and resources in caring for a child who displays aggressive behavior.3. Delineate the prognosis for children who have aggressive behaviors. PMID:21807873

  13. Investigating Three Explanations of Women's Relationship Aggression

    ERIC Educational Resources Information Center

    Graham-Kevan, Nicola; Archer, John

    2005-01-01

    This study investigated explanations of women's partner aggression in a sample of 358 women. Women completed measures of physical aggression, control, and fear. Three explanations of women's partner aggression were explored: (a) that its use is associated with fear, (b) that it is reciprocal, and (c) that it is coercive. Each explanation received…

  14. Fantasy Aggression and the Catharsis Phenomenon

    ERIC Educational Resources Information Center

    Spiegel, Sharon Baron; Zelin, Martin

    1973-01-01

    The purpose of this study was to explore the effects of fantasy aggression on blood pressure, affective states, and probability of subsequent aggression. The results are inconclusive because of the limited range of fantasy stimuli used and the short amount of time allowed for aggression to occur. (Author/KM)

  15. The myth of the aggressive monkey.

    PubMed

    Reinhardt, Viktor

    2002-01-01

    Captive rhesus macaques are not naturally aggressive, but poor husbandry and handling practices can trigger their aggression toward conspecifics and toward the human handler. The myth of the aggressive monkey probably is based on often not taking into account basic ethological principles when managing rhesus macaques in the research laboratory setting. PMID:16221082

  16. Female Aggression and Violence: A Case Study

    ERIC Educational Resources Information Center

    Martin, Penelope E.

    2012-01-01

    Aggression and violence among adolescent females has received extension attention throughout the nation. Girls often employ relationally aggressive behaviors to resolve conflict, which often leads to physical aggression. The purpose of this study was to examine a girl fight from multiple perspectives to gain a better understanding of the causes…

  17. Understanding and Preventing Aggressive Responses in Youth.

    ERIC Educational Resources Information Center

    Studer, Jeannine

    1996-01-01

    Fighting violence requires a networking approach among schools, community, and parents. This article advises elementary school counselors: (a) focus on the causes of aggression; (b) identify children with the propensity for behaving aggressively; and (c) prevent aggressive responses in children and adolescents by introducing techniques and…

  18. Relational Aggression among Middle School Girls

    ERIC Educational Resources Information Center

    Dallape, Aprille

    2008-01-01

    The purpose of this study was to examine the correlates that define relational aggression among middle school girls, the relationships among these factors, and the association between the correlates of relational aggression and the type of relational aggression (e.g., verbal, withdrawal) exhibited among middle school girls. The findings of this…

  19. Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders.

    PubMed

    Loechelt, Brett J; Green, Michael; Gottlieb, Peter A; Blumberg, Emily; Weinberg, Adriana; Quinlan, Scott; Baden, Lindsey R

    2015-09-01

    Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases. PMID:26336066

  20. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide.

    PubMed

    Damian, Diona L; Patterson, Clare R S; Stapelberg, Michael; Park, Joohong; Barnetson, Ross St C; Halliday, Gary M

    2008-02-01

    UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub PMID:17882270

  1. Feelings about Verbal Aggression: Justifications for Sending and Hurt from Receiving Verbally Aggressive Messages.

    ERIC Educational Resources Information Center

    Martin, Matthew M.; And Others

    1996-01-01

    Investigates whether receiving verbally aggressive messages was more hurtful depending on the source of the message; whether trait verbal aggression is justified; and whether the perceived hurt of verbally aggressive messages is related to a tendency to be verbally aggressive. Finds that messages from friends caused more hurt than messages from…

  2. Social Aggression on Television and Its Relationship to Children's Aggression in the Classroom

    ERIC Educational Resources Information Center

    Martins, Nicole; Wilson, Barbara J.

    2012-01-01

    A survey was conducted with over 500 children in grades K-5 to examine whether exposure to socially aggressive content was related to children's use of social aggression. The results of the survey revealed a significant relationship between exposure to televised social aggression and increased social aggression at school, but only for girls and…

  3. Effects of Aggressive vs. Nonaggressive Films on the Aggressive Behavior of Mentally Retarded Children.

    ERIC Educational Resources Information Center

    Evans, Charles

    Examined was the effect of viewing an aggressive film on the behavior of 22 moderately and mildly mentally retarded children (5-11 years old). Ss' doll playing was observed after they viewed a nonaggressive and an aggressive film. Results supported the hypothesis that Ss would exhibit more aggressive behavior following the aggressive than the…

  4. Association of Antibody Induction Immunosuppression with Cancer After Kidney Transplantation1

    PubMed Central

    Hall, Erin C; Engels, Eric A; Pfeiffer, Ruth M; Segev, Dorry L

    2014-01-01

    Background Induction immunosuppression is a mainstay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. Methods We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. 111,857 kidney recipients (1987–2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. cancer registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL)and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). Results 2,763 cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR=1.37, 95% CI 1.06–1.76). Alemtuzumab was associated with increased NHL (aIRR=1.79, 95% CI 1.02-1-3.14), colorectal cancer (aIRR=2.46, 95% CI 1.03–5.91), and thyroid cancer (aIRR=3.37, 95% CI 1.55–7.33). Polyclonal induction was associated with increased melanoma (aIRR=1.50, 95% CI 1.06–2.14). Conclusions Our findings highlight the relative safety with regard to cancer risk of the most common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T cell induction. PMID:25340595

  5. Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

    PubMed Central

    Castro-Manrreza, Marta E.; Mayani, Hector; Monroy-García, Alberto; Flores-Figueroa, Eugenia; Chávez-Rueda, Karina; Legorreta-Haquet, Victoria; Santiago-Osorio, Edelmiro

    2014-01-01

    Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM—the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BM-MSCs and UCB-MSCs significantly inhibited the proliferation of both CD4+ and CD8+ activated T cells in a cell–cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-γ, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4+CD25+CTLA-4+. Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications. PMID:24428376

  6. Characterization and Modulation of the Immunosuppressive Phase of Sepsis▿

    PubMed Central

    Muenzer, Jared T.; Davis, Christopher G.; Chang, Kathy; Schmidt, Robert E.; Dunne, W. Michael; Coopersmith, Craig M.; Hotchkiss, Richard S.

    2010-01-01

    Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had ∼40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-γ) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-γ production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies. PMID:20100863

  7. Characterization and modulation of the immunosuppressive phase of sepsis.

    PubMed

    Muenzer, Jared T; Davis, Christopher G; Chang, Kathy; Schmidt, Robert E; Dunne, W Michael; Coopersmith, Craig M; Hotchkiss, Richard S

    2010-04-01

    Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had approximately 40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-gamma) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-gamma production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies. PMID:20100863

  8. Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats.

    PubMed

    Tian, Honglei; Yan, Haiyan; Tan, Siwei; Zhan, Ping; Mao, Xiaoying; Wang, Peng; Wang, Zhouping

    2016-08-01

    The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL-12, and tumor necrosis factor-α (TNF-α) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide-associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the α-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression. PMID:27262314

  9. Cryptococcal cellulitis on the shin of an immunosuppressed patient.

    PubMed

    Zhu, Tian Hao; Rodriguez, Paola G; Behan, James W; Declerck, Brittney; Kim, Gene H

    2016-01-01

    Cryptococcus neoformans is a common fungus found throughout the environment that causes opportunistic disease in immunocompromised individuals. Infection of humans with C neoformans usually manifests as lung disease through inhalation of spores or meningoencephalitis by involvement of the central nervous system. Rarely, dissemination in the form of cutaneous lesions can occur in individuals with long term immunosuppression. We present a patient with C. neoformans manifesting as cellulitis with focal segmental glomerulosclerosis treated with corticosteroids. Because of the mortality associated with disseminated cryptococcosis, early identification, especially of atypical cutaneous presentations is critical from a dermatological perspective. PMID:27617599

  10. Research on the immunosuppressive activity of ingredients contained in sunscreens.

    PubMed

    Frikeche, Jihane; Couteau, Céline; Roussakis, Christos; Coiffard, Laurence J M

    2015-04-01

    The immunosuppressive properties of Benzophenone-4, an UV-filter and three ingredients, Allantoin, Bisabolol and Enoxolon used in sunscreen formulation, previously characterized as anti-inflammatory compounds, are studied. The results of this study demonstrate that four tested molecules have effects on DCs and T cells which are the most important cells of the immune system. The impact is also visible on keratinocyte cells which are in the direct contact with skin sunscreens. Each ingredient should be used with caution at reduced doses or even removed from some cosmetic preparations, such as sunscreens. PMID:25556843

  11. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  12. Weekly Paclitaxel/Carboplatin/Trastuzumab Therapy Improves Pathologic Complete Remission in Aggressive HER2-Positive Breast Cancers, Especially in Luminal-B Subtype, Compared With a Once-Every-3-Weeks Schedule

    PubMed Central

    Yu, Ke-Da; Liu, Guang-Yu; Chen, Can-Ming; Li, Jian-Wei; Wu, Jiong; Lu, Jin-Song; Shen, Zhen-Zhou

    2013-01-01

    Background. The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB–IIIC) breast cancers were evaluated in this phase II trial. Methods. Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2). Results. A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%–69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1–0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50). Conclusion. A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted. PMID:23635560

  13. Mapping Brain Development and Aggression

    PubMed Central

    Paus, Tomás

    2005-01-01

    Introduction This article provides an overview of the basic principles guiding research on brain-behaviour relationships in general, and as applied to studies of aggression during human development in particular. Method Key literature on magnetic resonance imaging of the structure and function of a developing brain was reviewed. Results The article begins with a brief introduction to the methodology of techniques used to map the developing brain, with a special emphasis on magnetic resonance imaging (MRI). It then reviews briefly the current knowledge of structural maturation, assessed by MRI, of the human brain during childhood and adolescence. The last part describes some of the results of neuroimaging studies aimed at identifying neural circuits involved in various aspects of aggression and social cognition. Conclusion The article concludes by discussing the potential and limitations of the neuroimaging approach in this field. PMID:19030495

  14. Preventing aggressive behaviour in dogs.

    PubMed

    Orritt, Rachel

    2016-07-01

    Delegates from around the world met at the University of Lincoln on June 11 and 12 for the third annual UK Dog Bite Prevention and Behaviour conference. The conference, hosted by dog trainer Victoria Stilwell, brings together dog behaviour experts to discuss possible solutions to this public health issue. Rachel Orritt, who has been examining the perceptions, assessment and management of human-directed aggressive behaviour in dogs for her PhD, reports. PMID:27389748

  15. Lateralization of aggression in fish.

    PubMed

    Bisazza, Angelo; de Santi, Andrea

    2003-05-15

    Recent research has suggested that lateralization of aggressive behaviors could follow an homogeneous pattern among all vertebrates. A left eye/right hemisphere dominance in eliciting aggressive responses has been demonstrated for all groups of tetrapods but teleost fish for which data is lacking. Here we studied differential eye use during aggressive interactions in three species of teleosts: Gambusia holbrooki, Xenotoca eiseni and Betta splendens. In the first experiment we checked for lateralization in the use of the eyes while the subject was attacking its own mirror image. In order to confirm the results, other tests were performed on two species and eye preference was scored during attacks or displays directed toward a live rival. All three species showed a marked preference for using the right eye when attacking a mirror image or a live rival. Thus, the direction of asymmetry in fish appears the opposite to that shown by all the other groups of vertebrates. Hypotheses on the origin of the difference are discussed. PMID:12742249

  16. Neurobiology of Aggression and Violence

    PubMed Central

    Siever, Larry J.

    2014-01-01

    Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of “top-down” control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of “top-down” control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/ gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance “top-down” control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic. PMID:18346997

  17. Rural neighborhoods and child aggression.

    PubMed

    Bowen, Natasha K; Wretman, Christopher J

    2014-12-01

    Structural equation modeling with latent variables was used to evaluate the direct and mediated effects of a neighborhood risk factor (negative teen behaviors) on the parent-report aggressive behavior of 213 students in grades 3 through 5 attending a school in a low-income, rural community. Contagion and social control hypotheses were examined as well as hypotheses about whether the neighborhood served as a microsystem or exosystem for rural pre-adolescents. Analyses took into account the clustering of students and ordinal nature of the data. Findings suggest that rural neighborhoods may operate as both a microsystem and exosystem for children, with direct contagion effects on their aggressive behaviors as well as indirect social control effects through parenting practices. Direct effects on aggression were also found for parenting practices and child reports of friends' negative behaviors. Pre-adolescence may be a transitional stage, when influences of the neighborhood on child behavior begin to compete with influences of caregivers. Findings can inform the timing and targets of violence prevention in rural communities. PMID:25205545

  18. Immunosuppressive nano-therapeutic micelles downregulate endothelial cell inflammation and immunogenicity

    PubMed Central

    Levey, Natalie; Esckilsen, Scott; Miller, Kayla; Dennis, William; Atkinson, Carl; Broome, Ann-Marie

    2015-01-01

    In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines. Uptake efficiency of TRaM nanoparticles was improved with the addition of a targeting moiety. In addition, our TRaM therapy was able to downregulate both mouse cardiac endothelial cell (MCEC) and HUVEC production and release of the pro-inflammatory cytokines, IL-6 and IL-8 in normal oxygen tension and hypoxic conditions. We were also able to demonstrate a dose-dependent uptake of TRaM therapy into biologic tissues ex vivo. Taken together, these data demonstrate the feasibility of targeted drug delivery in transplantation, which has the potential for conferring local immunosuppressive effects without systemic consequences while also dampening endothelial cell injury responses. PMID:26167278

  19. Cell therapy of refractory Crohn's disease.

    PubMed

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Ruchkina, I N; Konoplyannikov, A G

    2013-11-01

    We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy. PMID:24319711

  20. Antisocial personality disorder, alcohol, and aggression.

    PubMed

    Moeller, F G; Dougherty, D M

    2001-01-01

    Epidemiologic studies and laboratory research consistently link alcohol use with aggression. Not all people, however, exhibit increased aggression under the influence of alcohol. Recent research suggests that people with antisocial personality disorder (ASPD) may be more prone to alcohol-related aggression than people without ASPD. As a group, people with ASPD have higher rates of alcohol dependence and more alcohol-related problems than people without ASPD. Likewise, in laboratory studies, people with ASPD show greater increases in aggressive behavior after consuming alcohol than people without ASPD. The association between ASPD and alcohol-related aggression may result from biological factors, such as ASPD-related impairments in the functions of certain brain chemicals (e.g., serotonin) or in the activities of higher reasoning, or "executive," brain regions. Alternatively, the association between ASPD and alcohol-related aggression may stem from some as yet undetermined factor(s) that increase the risk for aggression in general. PMID:11496966

  1. REACTIVE AND PROACTIVE AGGRESSION IN ADOLESCENT MALES

    PubMed Central

    Fite, Paula J.; Raine, Adrian; Stouthamer-Loeber, Magda; Loeber, Rolf; Pardini, Dustin A.

    2010-01-01

    There is limited knowledge about the unique relations between adolescent reactive and proactive aggression and later psychosocial adjustment in early adulthood. Accordingly, this study prospectively examined associations between adolescent (mean age = 16) reactive and proactive aggression and psychopathic features, antisocial behavior, negative emotionality, and substance use measured 10 years later in early adulthood (mean age = 26). Study questions were examined in a longitudinal sample of 335 adolescent males. Path analyses indicate that after controlling for the stability of the outcome and the overlap between the two subtypes of aggression, reactive aggression is uniquely associated with negative emotionality, specifically anxiety, in adulthood. In contrast, proactive aggression is uniquely associated with measures of adult psychopathic features and antisocial behavior in adulthood. Both reactive and proactive aggression uniquely predicted substance use in adulthood, but the substances varied by subtype of aggression. Implications for findings are discussed. PMID:20589225

  2. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs. PMID:34189

  3. Aggression after Traumatic Brain Injury: Prevalence & Correlates

    PubMed Central

    Rao, Vani; Rosenberg, Paul; Bertrand, Melaine; Salehinia, Saeed; Spiro, Jennifer; Vaishnavi, Sandeep; Rastogi, Pramit; Noll, Kathy; Schretlen, David J; Brandt, Jason; Cornwell, Edward; Makley, Michael; Miles, Quincy Samus

    2010-01-01

    Aggression after traumatic brain injury (TBI) is common but not well defined. Sixty-seven participants with first-time TBI were seen within three months of injury and evaluated for aggression. The prevalence of aggression was found to be 28.4% and to be predominantly verbal aggression. Post-TBI aggression was associated with new-onset major depression (p=0.02), poorer social functioning (p=0.04), and increased dependency on activities of daily living (p=0.03), but not with a history of substance abuse or adult/childhood behavioral problems. Implications of the study include early screening for aggression, evaluation for depression, and consideration of psychosocial support in aggressive patients. PMID:19996251

  4. Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma

    PubMed Central

    Gisselbrecht, Christian; Schmitz, Norbert; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Milpied, Noel J.; Radford, John; Ketterer, Nicolas; Shpilberg, Ofer; Dührsen, Ulrich; Hagberg, Hans; Ma, David D.; Viardot, Andreas; Lowenthal, Ray; Brière, Josette; Salles, Gilles; Moskowitz, Craig H.; Glass, Bertram

    2012-01-01

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT. PMID:23091101

  5. In vivo indomethacin reverse exercise-induced immunosuppression in rats.

    PubMed

    Asselin, P; Benquet, C; Krzystyniak, K; Brousseau, P; Savard, R; Fournier, M

    1996-01-01

    The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis. PMID:9023588

  6. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum.

    PubMed

    Tian, Yufeng; Chen, Wenlin; Mo, Guoxiang; Chen, Ran; Fang, Mingqian; Yedid, Gabriel; Yan, Xiuwen

    2016-01-01

    Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1-2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts' immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA). In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) and interferon-gamma (IFN-γ). In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS) alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL). Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL) in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks' successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear. PMID:27153086

  7. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum

    PubMed Central

    Tian, Yufeng; Chen, Wenlin; Mo, Guoxiang; Chen, Ran; Fang, Mingqian; Yedid, Gabriel; Yan, Xiuwen

    2016-01-01

    Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1–2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts’ immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA). In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) and interferon-gamma (IFN-γ). In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS) alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL). Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL) in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks’ successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear. PMID:27153086

  8. Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells.

    PubMed

    Terme, Magali; Ullrich, Evelyn; Aymeric, Laetitia; Meinhardt, Kathrin; Coudert, Jérôme D; Desbois, Mélanie; Ghiringhelli, François; Viaud, Sophie; Ryffel, Bernard; Yagita, Hideo; Chen, Lieping; Mécheri, Salaheddine; Kaplanski, Gilles; Prévost-Blondel, Armelle; Kato, Masashi; Schultze, Joachim L; Tartour, Eric; Kroemer, Guido; Degli-Esposti, Mariapia; Chaput, Nathalie; Zitvogel, Laurence

    2012-06-01

    During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice. PMID:22427351

  9. IL-18 induces PD-1-dependent immunosuppression in cancer.

    PubMed

    Terme, Magali; Ullrich, Evelyn; Aymeric, Laetitia; Meinhardt, Kathrin; Desbois, Mélanie; Delahaye, Nicolas; Viaud, Sophie; Ryffel, Bernard; Yagita, Hideo; Kaplanski, Gilles; Prévost-Blondel, Armelle; Kato, Masashi; Schultze, Joachim L; Tartour, Eric; Kroemer, Guido; Chaput, Nathalie; Zitvogel, Laurence

    2011-08-15

    Immunosuppressive cytokines subvert innate and adaptive immune responses during cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to accumulate in cancer patients, but its pathophysiological role remains unclear. In this study, we show that low levels of circulating IL-18, either exogenous or tumor derived, act to suppress the NK cell arm of tumor immunosurveillance. IL-18 produced by tumor cells promotes the development of NK-controlled metastases in a PD-1-dependent manner. Accordingly, PD-1 is expressed by activated mature NK cells in lymphoid organs of tumor bearers and is upregulated by IL-18. RNAi-mediated knockdown of IL-18 in tumors, or its systemic depletion by IL-18-binding protein, are sufficient to stimulate NK cell-dependent immunosurveillance in various tumor models. Together, these results define IL-18 as an immunosuppressive cytokine in cancer. Our findings suggest novel clinical implementations of anti-PD-1 antibodies in human malignancies that produce IL-18. PMID:21724589

  10. Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

    PubMed Central

    Yang, Hong; Zhao, Guang-Yue; Zhang, Geng; Lu, Zhi-Hong; Huang, Yan-Hong; Ma, Xiang-Dong; Liu, Hai-Xia; Liang, Sheng-Ru; Yang, Fang; Chen, Bi-Liang

    2013-01-01

    Objective To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. Methods In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. Results Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. Conclusion We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research. PMID:24278415

  11. Fatal Myocarditis Associated With HHV-6 Following Immunosuppression in Two Children.

    PubMed

    Stefanski, Heather E; Thibert, Kathryn A; Pritchett, Joshua; Prusty, Bhupesh K; Wagner, John E; Lund, Troy C

    2016-01-01

    Fatal myocarditis is a rare complication in immunosuppressed children. Recent reports have linked human herpesvirus 6 (HHV-6) infection, typically a benign infection in childhood, with myocarditis. HHV-6 can reactivate during periods of immunosuppression. Here, we report 2 cases in which children were immunosuppressed, one for treatment of Evans syndrome and the other post hematopoietic stem cell transplantation, who developed rapid and fatal HHV-6-associated myocarditis. These cases suggest that HHV-6 infection should be considered as an etiology of myocarditis in immunosuppressed patients regardless of correlating blood levels. Early treatment of HHV-6 in patients with myocarditis could improve morbidity and mortality. PMID:26681781

  12. Student nurses' perceptions of aggression: An exploratory study of defensive styles, aggression experiences, and demographic factors.

    PubMed

    Bilgin, Hulya; Keser Ozcan, Neslihan; Tulek, Zeliha; Kaya, Fadime; Boyacioglu, Nur Elcin; Erol, Ozgul; Arguvanli Coban, Sibel; Pazvantoglu, Ozan; Gumus, Kubra

    2016-06-01

    Throughout the clinical learning process, nursing students' perception of aggression might have implications in terms of their future professional behavior toward patients. Using a descriptive cross-sectional design, we investigated the relationships between student nurses' perceptions of aggression and their personal characteristics, defense styles, and a convenience sample of 1539 experiences of aggressive behavior in clinical practice. Information about the students' personal features, their clinical practice, and experiences of aggressive behavior was obtained by questionnaire. The Turkish version of the Perception of Aggression Scale and Defense Styles Questionnaire-40 were also used. Students were frequently exposed to verbal aggression from patients and their relatives. And perceived patient aggression negatively, perception of aggression were associated with sex, defense styles, feelings of safety, and experiences of aggressions during clinical practice. Of interest is the reality that student nurses should be prepared for untoward events during their training. PMID:26916604

  13. Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

    SciTech Connect

    Lee, Won-Jae; Hah, Young-Sool; Ock, Sun-A.; Lee, Jae-Hoon; Jeon, Ryong-Hoon; Park, Ji-Sung; Lee, Sang-Il; Rho, Na-Young; Rho, Gyu-Jin; Lee, Sung-Lim

    2015-05-01

    The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice. - Highlights: • Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. • Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. • SF-MSCs exhibited improved therapeutic effects than BM-MSCs. • SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases.

  14. Psychopharmacological treatment of aggression in schizophrenic patients.

    PubMed

    Brieden, T; Ujeyl, M; Naber, D

    2002-05-01

    Aggressive behavior is frequently observed in schizophrenic patients. More than 50 % of all psychiatric patients and 10 % of schizophrenic patients show aggressive symptoms varying from threatening behavior and agitation to assault. The pharmacological treatment of acute, persisting and repetitive aggression is a serious problem for other patients and staff members. Not only is violent behavior from mentally ill patients the most detrimental factor in their stigmatization, aggression is also a considerable direct source of danger for the patients themselves. Based on rather limited evidence, a wide variety of medications for the pharmacological treatment of aggression has been recommended: typical and atypical antipsychotics, benzodiazepines, mood stabilizers, beta-blockers and selective serotonin reuptake inhibitors (SSRIs). Most clinical information on treating aggression has been collected for atypical neuroleptics, particularly for clozapine. Several retrospective and open studies indicate its efficacy. Treatment duration of 6 months is recommended to induce a stable reduction of physical and verbal aggression. Severe side effects have very rarely been seen. At the moment, clozapine seems to be the first choice in aggression treatment. Within the last few years, about 10 articles were published showing that this is the most effective antiaggressive agent in the treatment of aggression and agitation in psychiatric patients, independent of psychiatric diagnosis. However, clozapine, like all the other substances used, does not have an established indication for the treatment of aggressive symptoms. Noncompliance with medication makes it difficult to choose the right preparation for the medication: tablets, liquids, intramuscular injections and readily soluble "FDDFs" are available. Ethical, juridical and methodological problems prevent controlled studies from establishing a reference in the treatment of aggression in mentally ill patients. This review summarizes

  15. The passive-aggressive organization.

    PubMed

    Kaplan, Robert S; Norton, David P

    2005-10-01

    Passive-aggressive organizations are friendly places to work: People are congenial, conflict is rare, and consensus is easy to reach. But, at the end of the day, even the best proposals fail to gain traction, and a company can go nowhere so imperturbably that it's easy to pretend everything is fine. Such companies are not necessarily saddled with mulishly passive-aggressive employees. Rather, they are filled with mostly well-intentioned people who are the victirms of flawed processes and policies. Commonly, a growing company's halfhearted or poorly thought-out attempts to decentralize give rise to multiple layers of managers, whose authority for making decisions becomes increasingly unclear. Some managers, as a result, hang back, while others won't own up to the calls they've made, inviting colleagues to second-guess or overturn the decisions. In such organizations, information does not circulate freely, and that makes it difficult for workers to understand the impact of their actions on company performance and for managers to correctly appraise employees' value to the organization. A failure to accurately match incentives to performance stifles initiative, and people do just enough to get by. Breaking free from this pattern is hard; a long history of seeing corporate initiatives ignored and then fade away tends to make people cynical. Often it's best to bring in an outsider to signal that this time things will be different. He or she will need to address every obstacle all at once: clarify decision rights; see to it that decisions stick; and reward people for sharing information and adding value, not for successfully negotiating corporate politics. If those steps are not taken, it's only a matter of time before the diseased elements of a passive-aggressive organization overwhelm the remaining healthy ones and drive the company into financial distress. PMID:16250627

  16. Aggressive Angiomyxoma with Perineal Herniation

    PubMed Central

    Narang, Seema; Kohli, Supreethi; Kumar, Vinod; Chandoke, Raj

    2014-01-01

    Aggressive angiomyxoma is a rare mesenchymal tumor involving the pelvic-perineal region. It occurs during the third and fourth decade of life and is predominantly seen in females. It presents clinically as a soft tissue mass in variable locations such as vulva, perianal region, buttock, or pelvis. Assessment of extent of the tumor by radiological evaluation is crucial for surgical planning; however, biopsy is essential to establish diagnosis. We present the radiological and pathological features seen in a 43-year-old female diagnosed with abdominal angiomyxoma with an unusual extension to the perineum. PMID:24987570

  17. Problems in the study of rodent aggression.

    PubMed

    Blanchard, Robert J; Wall, Philip M; Blanchard, D Caroline

    2003-09-01

    Laboratory research has produced detailed descriptions of aggression and defense patterns in the rat, mouse, and hamster, showing strong similarities, but also some differences, across these species. Research on target sites for attack, in conjunction with analyses of the situational antecedents of attack behaviors and of responsivity of these to conditions that elicit fear, has also provided a strong basis for analysis of offensive and defensive aggression strategies and for identification of combinations of these modalities such as may occur in maternal aggression. These patterns have been empirically differentiated from phenomena such as play fighting or predation and compared for laboratory rodents and their wild ancestors. An array of tasks, suitable for use with pharmacological and experimental manipulations, is available for analysis of both aggression and defense. These developments should produce a firm basis for research using animal models to analyze a broad array of aggression-related phenomena, including systematic approaches to understanding the normal antecedents and consequences of each of several differentiable types of aggressive behavior. Despite this strong empirical and analytic background, laboratory animal aggression research has been in a period of decline, spanning several decades, relative to comparable research focusing on areas such as sexual behavior or stress. Problems that may have contributed to the relative neglect of aggression research include confusion about the interpretation of different tasks for eliciting aggression; difficulties and labor intensiveness of observational measures needed for an adequate differentiation of offensive and defensive behaviors; analytic difficulties stemming from the sensitivity of offensive aggression to the inhibitory effects of fear or defensiveness; lack of a clear relationship between categories of aggressive behavior as defined in animal studies and those used in human aggression research; and

  18. The short-term impact of protocol biopsies in a live-related renal transplant program using tacrolimus based immunosuppression.

    PubMed

    Guleria, S; Jain, S; Dinda, A K; Mahajan, S; Gupta, S; Mehra, N K

    2013-07-01

    The aim of the study was to assess the impact of protocol biopsies in a live-related renal transplant program using tacrolimus-based immunosuppression in the short term. Eighty-three live-related transplant recipients were randomly allocated to protocol biopsy group (Group I, n = 40) and a control group (Group II, n = 43). Other immunosuppressants in these groups consisted of either mycophenolate mofetil or azathioprine and steroids. Protocol biopsies were conducted in biopsy group at 1, 6, and 12 months post-transplant. The non-biopsy group was followed by serial serum creatinine and biopsies in them were conducted as and when clinically indicated. Both groups were analyzed at 12 months with respect to graft function and survival. The two groups were similar with respect to age, number of dialysis pre-operatively, tacrolimus levels, induction therapy, donor age, and donor glomerular filtration rate. Forty protocol biopsies were conducted at 1 month, 31 at 6 months, and 26 at 12 months. The prevalence of sub-clinical rejection at 1, 6, and 12 months in these biopsies was 17.5%, 11.2%, and 10.3%, respectively. The prevalence of calcineurin inhibitor toxicity during same period was 15%, 15.5%, and 14.4%, respectively. The cumulative rejection rate in Group I and Group II at 12-month follow-up was 10.3% and 11.3% (P = 0.78), respectively, and cumulative calcineurin inhibitor toxicity at 12 months was 14.4% and 9.3% (P = 0.59), respectively, were not statistically significant. There was no difference in graft survival and function at 1 year. Protocol biopsies have a limited role in a well-matched renal transplant program with tacrolimus-based immunosuppression in the short term. However, the long-term impact of protocol biopsies needs further evaluation. PMID:23960339

  19. Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated with immunosuppressants: a French retrospective multicenter study.

    PubMed

    Bauer, Hélène; Luxembourger, Cécile; Gottenberg, Jacques-Eric; Fournier, Sophie; Abravanel, Florence; Cantagrel, Alain; Chatelus, Emmanuel; Claudepierre, Pascal; Hudry, Christophe; Izopet, Jacques; Fabre, Sylvie; Lefevre, Guillaume; Marguerie, Laurent; Martin, Antoine; Messer, Laurent; Molto, Anna; Pallot-Prades, Béatrice; Pers, Yves-Marie; Roque-Afonso, Anne-Marie; Roux, Christian; Sordet, Christelle; Soubrier, Martin; Veissier, Claire; Wendling, Daniel; Péron, Jean-Marie; Sibilia, Jean

    2015-04-01

    The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2-20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3-55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure. PMID:25860212

  20. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  1. What lies beneath the face of aggression?

    PubMed

    Carré, Justin M; Murphy, Kelly R; Hariri, Ahmad R

    2013-02-01

    Recent evidence indicates that a sexually dimorphic feature of humans, the facial width-to-height ratio (FWHR), is positively correlated with reactive aggression, particularly in men. Also, predictions about the aggressive tendencies of others faithfully map onto FWHR in the absence of explicit awareness of this metric. Here, we provide the first evidence that amygdala reactivity to social signals of interpersonal challenge may underlie the link between aggression and the FWHR. Specifically, amygdala reactivity to angry faces was positively correlated with aggression, but only among men with relatively large FWHRs. The patterns of association were specific to angry facial expressions and unique to men. These links may reflect the common influence of pubertal testosterone on craniofacial growth and development of neural circuitry underlying aggression. Amygdala reactivity may also represent a plausible pathway through which FWHR may have evolved to represent an honest indicator of conspecific threat, namely by reflecting the responsiveness of neural circuitry mediating aggressive behavior. PMID:22198969

  2. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. PMID:26216041

  3. [Pregnancy following liver transplantation and during immunosuppression with cyclosporine].

    PubMed

    Günter, H H; Mauz, S; Ringe, B; Niesert, S

    1990-05-11

    Orthotopic liver transplantation had been performed in 1983 in a now 40-year-old woman in the terminal stage of posthepatitis liver cirrhosis with recurrent oesophageal bleedings and precoma from complete liver-cell failure. She became pregnant in 1988 while under immunosuppression with cyclosporin (2.1-2.7 mg/kg body-weight) and prednisolone (5 or 7.5 mg daily in rotation). Pregnancy proceeded without complication and there were no side effects from cyclosporin. After premature membrane rupture in the 39th week of pregnancy uterine inertia developed during oxytocin stimulation of contractions, and caesarean section was performed. The female infant was normally developed without any malformations. Liver, kidney and adrenal functions were normal, as was haemopoiesis. But possible late sequelae of cyclosporin treatment in the child cannot as yet be assessed because of the short follow-up. PMID:2338057

  4. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  5. Multiple overlapping homologies between two rheumatoid antigens and immunosuppressive viruses.

    PubMed Central

    Douvas, A; Sobelman, S

    1991-01-01

    Amino acid (aa) sequence homologies between viruses and autoimmune nuclear antigens are suggestive of viral involvement in disorders such as systemic lupus erythematosus (SLE) and scleroderma. We analyzed the frequency of exact homologies of greater than or equal to 5 aa between 61 viral proteins (19,827 aa), 8 nuclear antigens (3813 aa), and 41 control proteins (11,743 aa). Both pentamer and hexamer homologies between control proteins and viruses are unexpectedly abundant, with hexamer matches occurring in 1 of 3 control proteins (or once every 769 aa). However, 2 nuclear antigens, the SLE-associated 70-kDa antigen and the scleroderma-associated CENP-B protein, are highly unusual in containing multiple homologies to a group of synergizing immunosuppressive viruses. Two viruses, herpes simplex virus 1 (HSV-1) and human immunodeficiency virus 1 (HIV-1), contain sequences exactly duplicated at 15 sites in the 70-kDa antigen and at 10 sites in CENP-B protein. The immediate-early (IE) protein of HSV-1, which activates HIV-1 regulatory functions, contains three homologies to the 70-kDa antigen (two hexamers and a pentamer) and two to CENP-B (a hexamer and pentamer). There are four homologies (including a hexamer) common to the 70-kDa antigen and Epstein-Barr virus, and three homologies (including two hexamers) common to CENP-B and cytomegalovirus. The majority of homologies in both nuclear antigens are clustered in highly charged C-terminal domains containing epitopes for human autoantibodies. Furthermore, most homologies have a contiguous or overlapping distribution, thereby creating a high density of potential epitopes. In addition to the exact homologies tabulated, motifs of matching sequences are repeated frequently in these domains. Our analysis suggests that coexpression of heterologous viruses having common immunosuppressive functions may generate autoantibodies cross-reacting with certain nuclear proteins. PMID:1712488

  6. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    PubMed Central

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  7. Immunosuppressive treatment protects against angiotensin II-induced renal damage.

    PubMed

    Muller, Dominik N; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C

    2002-11-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-alpha on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-alpha receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-kappaB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-alpha is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  8. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage

    PubMed Central

    Muller, Dominik N.; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C.

    2002-01-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-α on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-α receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-κB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-α is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  9. Calpains: markers of tumor aggressiveness?

    PubMed

    Roumes, Hélène; Leloup, Ludovic; Dargelos, Elise; Brustis, Jean-Jacques; Daury, Laetitia; Cottin, Patrick

    2010-05-15

    Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are mu-calpain and m-calpain. Study of calpain expression and activity underline the deregulation of calpain activity in RMS. Analysis of kinetic characteristics of RMS cells, compared to human myoblasts LHCN-M2 cells, shows an important migration velocity in RMS cells. One of the major results of this study is the positive linear correlation between calpain activity and migration velocity presenting calpains as a marker of tumor aggressiveness. The RMS cytoskeleton is disorganized. Specifying the role of mu- and m-calpain using antisense oligonucleotides led to show that both calpains up-regulate alpha- and beta-actin in ARMS cells. Moreover, the invasive behavior of these cells is higher than that of LHCN-M2 cells. However, it is similar to that of non-treated LHCN-M2 cells, when calpains are inhibited. In summary, calpains may be involved in the anarchic adhesion, migration and invasion of RMS. The direct relationship between calpain activity and migration velocities or invasive behavior indicates that calpains could be considered as markers of tumor aggressiveness and as potential targets for limiting development of RMS tumor as well as their metastatic behavior. PMID:20193680

  10. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis

    PubMed Central

    Palejwala, Sheri K.; Zangeneh, Tirdad T.; Goldstein, Stephen A.; Lemole, G. Michael

    2016-01-01

    Background: Rhinocerebral mucormycosis occurs in immunocompromised hosts with uncontrolled diabetes, solid organ transplants, and hematologic malignancies. Primary disease is in the paranasal sinuses but often progresses intracranially, via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal with a mortality rate of 85%, even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes. Methods: We performed a retrospective chart review of patients with rhinocerebral mucormycosis from 2011 to 2014. These patients were analyzed for symptoms, surgical and medical management, and outcome. We found four patients who were diagnosed with rhinocerebral mucormycosis. All patients underwent rapid aggressive surgical debridement and were started on antifungal therapy on the day of diagnosis. Overall, we observed a mortality rate of 50%. Results: An early aggressive multidisciplinary approach with surgical debridement, antifungal therapy, and correction of underlying disease have been shown to improve survivability in rhinocerebral mucormycosis. Conclusion: A multidisciplinary approach to rhinocerebral mucormycosis with otolaryngology, neurosurgery, and ophthalmology, infectious disease and medical intensivists can help reduce mortality in an otherwise largely fatal disease. Even despite these measures, outcomes remain poor, and a high index of suspicion must be maintained in at-risk populations, in order to rapidly execute a multifaceted approach. PMID:27280057

  11. Emerging therapies for treatment of multiple sclerosis

    PubMed Central

    Corboy, John R; Miravalle, Augusto A

    2010-01-01

    In the last decade, a new armamentarium of immune-based therapies have been developed and tested in patients with multiple sclerosis. Some of these therapies are showing a high level of efficacy, with an acceptable adverse effect profile. Because present therapies have significant limitations in slowing disease progression, require injections, are sometimes associated with significant side effects of immunosuppression, and do little to reverse disability, identifying more effective treatments is an important goal for clinical research in multiple sclerosis. However, in order to improve our current approach to disease-modifying therapies, it is imperative to promote the development of individualized therapy strategies. PMID:22096357

  12. Men’s Aggression Toward Women

    PubMed Central

    Kim, Hyoun K.; Laurent, Heidemarie K.; Capaldi, Deborah M.; Feingold, Alan

    2008-01-01

    The present study examined the longitudinal course of men’s physical and psychological aggression toward a partner across 10 years, using a community sample of young couples (N = 194) from at-risk backgrounds. Findings indicated that men’s aggression decreased over time and that women’s antisocial behavior and depressive symptoms predicted changes in men’s aggression. This suggests the importance of studying social processes within the dyad to have a better understanding of men’s aggression toward a partner. PMID:19122790

  13. Neural control of aggression in Drosophila.

    PubMed

    Hoopfer, Eric D

    2016-06-01

    Like most animal species, fruit flies fight to obtain and defend resources essential to survival and reproduction. Aggressive behavior in Drosophila is genetically specified and also strongly influenced by the fly's social context, past experiences and internal states, making it an excellent framework for investigating the neural mechanisms that regulate complex social behaviors. Here, I summarize our current knowledge of the neural control of aggression in Drosophila and discuss recent advances in understanding the sensory pathways that influence the decision to fight or court, the neuromodulatory control of aggression, the neural basis by which internal states can influence both fighting and courtship, and how social experience modifies aggressive behavior. PMID:27179788

  14. Aggression and coexistence in female caribou

    USGS Publications Warehouse

    Weckerly, Floyd W.; Ricca, Mark A.

    2014-01-01

    Female caribou (Rangifer tarandus) are highly gregarious, yet there has been little study of the behavioral mechanisms that foster coexistence. Quantifying patterns of aggression between male and female, particularly in the only cervid taxa where both sexes grow antlers, should provide insight into these mechanisms. We asked if patterns of aggression by male and female caribou followed the pattern typically noted in other polygynous cervids, in which males display higher frequencies and intensity of aggression. From June to August in 2011 and 2012, we measured the frequency and intensity of aggression across a range of group sizes through focal animal sampling of 170 caribou (64 males and 106 females) on Adak Island in the Aleutian Archipelago, Alaska. Males in same-sex and mixed-sex groups and females in mixed-sex groups had higher frequencies of aggression than females in same-sex groups. Group size did not influence frequency of aggression. Males displayed more intense aggression than females. Frequent aggression in mixed-sex groups probably reflects lower tolerance of males for animals in close proximity. Female caribou were less aggressive and more gregarious than males, as in other polygynous cervid species.

  15. Video media-induced aggressiveness in children.

    PubMed

    Cardwell, Michael Steven

    2013-09-01

    Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented. PMID:24002556

  16. Gibbon Aggression During Introductions: An International Survey.

    PubMed

    Harl, Heather; Stevens, Lisa; Margulis, Susan W; Petersen, Jay

    2016-01-01

    Little is known regarding the prevalence of aggression seen during introductions of captive gibbons (Hylobatidae). In this study, an online survey was developed to quantify and collect contextual details regarding the frequency and types of aggression seen during introductions of captive gibbons (Hylobatidae). Nineteen percent of institutions (17 institutions) reported observing aggression, and 6 of these institutions recorded multiple instances of aggression, though a vast majority of these cases resulted in mild injuries or none at all. The female was the primary aggressor in 23% of cases, the male was the primary aggressor in 58% of cases, and both were the primary aggressor in 1 case. Although these aggressive interactions were often not associated with a known cause, 27% of cases were associated with food displacement. In most cases, management changes, including trying new pairings, greatly reduced situational aggression, suggesting that individual personalities may play a factor in aggression. These data begin to explain the extent of aggression observed in captive gibbons; future studies will address possible correlations with aggression and introduction techniques. PMID:26963568

  17. Intimate partner aggression and women's work outcomes.

    PubMed

    LeBlanc, Manon Mireille; Barling, Julian; Turner, Nick

    2014-10-01

    Using conservation of resources theory, we examined the relationship between intimate partner aggression enacted against heterosexual women and 3 types of work-related outcomes for these women: withdrawal while at work (i.e., cognitive distraction, work neglect), withdrawal from work (i.e., partial absenteeism, intentions to quit), and performance. In Study 1, we compared withdrawal both at and from work across 3 clinically categorized groups of women (n = 50), showing that experiencing physical aggression is related to higher work neglect. We replicated and extended these findings in Study 2 using a community sample of employed women (n = 249) by considering the incremental variance explained by both physical aggression and psychological aggression on these same outcomes. Results showed that physical aggression predicted higher levels of withdrawal both at and from work, with psychological aggression predicting additional variance in partial absenteeism over and above the effects of physical aggression. Study 3 extended the model to include academic performance as an outcome in a sample of female college students (n = 122) in dating relationships. Controlling for the women's conscientiousness, psychological aggression predicted lower academic performance after accounting for the effects of physical aggression. We discuss theoretical and practical implications of these results, as well as directions for future research. PMID:25068818

  18. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders

    PubMed Central

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-01-01

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system’s ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD. PMID:26600976

  19. Effects of viewing relational aggression on television on aggressive behavior in adolescents: A three-year longitudinal study.

    PubMed

    Coyne, Sarah M

    2016-02-01

    Most researchers on media and aggression have examined the behavioral effects of viewing physical aggression in the media. Conversely, in the current study, I examined longitudinal associations between viewing relational aggression on TV and subsequent aggressive behavior. Participants included 467 adolescents who completed a number of different questionnaires involving media and aggression at 3 different time points. Results revealed that viewing relational aggression on TV was longitudinally associated with future relational aggression. However, early levels of relational aggression did not predict future exposure to televised relational aggression. Conversely, there was a bidirectional relationship between TV violence and physical aggression over time. No longitudinal evidence was found for a general effect of viewing TV, as all significant media effects were specific to the type of aggression viewed. These results support the general aggression model and suggest that viewing relational aggression in the media can have a long-term effect on aggressive behavior during adolescence. PMID:26595354

  20. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  1. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  2. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    PubMed

    ElShamy, Wael M; Sinha, Abhilasha; Said, Neveen

    2016-01-01

    The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the "aggressiveness niche" and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche. PMID:27493669

  3. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    PubMed Central

    2016-01-01

    The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the “aggressiveness niche” and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche. PMID:27493669

  4. Response to primary infection with Herpesvirus saimiri in immunosuppressed juvenile and newborn squirrel monkeys.

    PubMed Central

    Martin, L N; Allen, W P

    1975-01-01

    Immunosuppression of juvenile squirrel monkeys with combined azathioprine, prednisolone, and antilymphocyte globulin resulted in decreased antibody responses to viral antigens after primary infection with Herpesvirus saimiri (HVS). The virus was repeatedly isolated from the oropharynx of immunosuppressed monkeys but not from untreated infected controls. Thus immune factors are important in inhibiting shedding of HVS from the oropharynx. HVS could be isolated from the peripheral blood lymphocytes of infected control monkeys but not from the lymphocytes of immunosuppressed monkeys. Immunosuppressed monkeys also had decreased percentages of lymphocytes capable of forming rosettes with sheep erythrocytes. These results indicate that the immunosuppressive agents had inhibitory effects on lymphocytes (presumably thymus derived) capable of being latently infected with HVS. Antibody responses in newborn monkeys infected with HVS were delayed compared with juvenile monkeys. Treatment of newborn monkeys with antilymphocyte globulin had no suppressive effect on antibody responses to HVS. PMID:170204

  5. Regression of advanced melanoma upon withdrawal of immunosuppression: case series and literature review

    PubMed Central

    Thomas, N.; Sharpless, N.; Collichio, F.

    2013-01-01

    We report two cases of stage IV malignant melanoma arising in patients treated with azathioprine for myasthenia gravis. In both cases, the melanoma metastases regressed upon withdrawal of immunosuppression. One patient remains melanoma free at 10 years, and the second patient experienced an 18-month disease free period. There is one prior case report in the medical literature to support full immune reconstitution for treatment in advanced immunosuppression-related melanoma, and one case series suggesting that transplant patients developing melanoma may benefit from a switch to sirolimus. Virtually, no data exist for the medical management of early stage melanoma in the immunosuppressed patients. We review the limited preclinical data in support of immune reconstitution and the data on immunosuppression as a risk factor for melanoma. We conclude that reduction or withdrawal of immunosuppression may be beneficial in patients with advanced stage melanoma and warrants further consideration in patients with early stage melanoma. PMID:19890737

  6. Immunosuppressive Mechanisms of Malignant Gliomas: Parallels at Non-CNS Sites

    PubMed Central

    Perng, Powell; Lim, Michael

    2015-01-01

    The central nervous system (CNS) possesses powerful local and global immunosuppressive capabilities that modulate unwanted inflammatory reactions in nervous tissue. These same immune-modulatory mechanisms are also co-opted by malignant brain tumors and pose a formidable challenge to brain tumor immunotherapy. Routes by which malignant gliomas coordinate immunosuppression include the mechanical and functional barriers of the CNS; immunosuppressive cytokines and catabolites; immune checkpoint molecules; tumor-infiltrating immune cells; and suppressor immune cells. The challenges to overcoming tumor-induced immunosuppression, however, are not unique to the brain, and several analogous immunosuppressive mechanisms also exist for primary tumors outside of the CNS. Ultimately, the immune responses in the CNS are linked and complementary to immune processes in the periphery, and advances in tumor immunotherapy in peripheral sites may therefore illuminate novel approaches to brain tumor immunotherapy, and vice versa. PMID:26217588

  7. Dystrophin conferral using human endothelium expressing HLA-E in the non-immunosuppressive murine model of Duchenne muscular dystrophy.

    PubMed

    Cui, Chang-Hao; Miyoshi, Shunichiro; Tsuji, Hiroko; Makino, Hatsune; Kanzaki, Seiichi; Kami, Daisuke; Terai, Masanori; Suzuki, Harumi; Umezawa, Akihiro

    2011-01-15

    Human leukocyte antigen (HLA)-E is a non-classical major histocompatibility complex class I (Ib) molecule, which plays an important role in immunosuppression. In this study, we investigated the immunomodulating effect of HLA-E in a xenogeneic system, using human placental artery-derived endothelial (hPAE) cells expressing HLA-E in a mouse model. In vitro cell lysis analysis by primed lymphocytes in combination with siRNA transfection showed that HLA-E is necessary for inhibition of the immune response. Similarly, in vivo cell implantation analysis with siRNA-mediated down-regulation of HLA-E demonstrates that HLA-E is involved in immunosuppression. As hPAE cells efficiently transdifferentiate into myoblasts/myocytes in vitro, we transplanted the cells into mdx mice, a model of Duchenne muscular dystrophy. hPAE cells conferred dystrophin to myocytes of the 'immunocompetent' mdx mice with extremely high efficiency. These findings suggest that HLA-E-expressing cells with a myogenic potential represent a promising source for cell-based therapy of patients with muscular dystrophy. PMID:20947660

  8. Immunosuppression of breast cancer cells mediated by transforming growth factor-β in exosomes from cancer cells

    PubMed Central

    RONG, LEI; LI, RONG; LI, SHAOYING; LUO, RONGCHENG

    2016-01-01

    Exosomes derived from tumor cells are essential for processes involved in tumor progression, including angiogenesis, tumor cell proliferation and immunoregulation. In addition, exosome secretion may contribute to the mechanisms of hypoxia-induced angiogenesis and metastasis of tumors. In the present study, as it is one of the most common cancers in females, breast cancer, cell lines were cultured under hypoxic (1% O2) and normoxic conditions to evaluate the effects of hypoxia on exosome production. Under hypoxic conditions an increase in the number of exosomes in the medium, determined by CD63 immunoblotting, was observed. Application of these exosomes to T cells revealed that they were able to suppress T cell proliferation. As transforming growth factor-β (TGF-β), interleukin-10, and prostaglandin E2 are important factors in the mediation of T cell suppression, the exosomes were subsequently treated with antibodies against these three factors. The results revealed that anti-TGF-β was capable of ameliorating the immunosuppressive effects of exosomes. These data demonstrate that hypoxia enhances the secretion of exosomes by breast cancer cells, which acts to suppress T cell proliferation via TGF-β. The findings have significant implications for understanding the underlying mechanisms of immunosuppression in tumor microenvironments, and for the potential development of cancer therapies. PMID:26870240

  9. Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

    PubMed

    Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

    2015-11-01

    Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS. PMID:26125605

  10. Post-transplantation primary central nervous system lymphoma in a patient with systemic lupus erythematosus and prolonged use of immunosuppressant.

    PubMed

    Tse, Teresa P K; Chan, Allan N L; Chan, Tony K T; Po, Y C

    2014-12-01

    Post-transplantation primary central nervous system lymphoma is an uncommon and fatal post-transplant lymphoproliferative disorder. Such lymphomas have been described in only a few case series in the literature. The incidence of this condition is rising with improved survival after organ transplantation. A case of post-transplantation primary central nervous system lymphoma in a young Chinese woman with systemic lupus erythematosus is described here. She presented with right-sided weakness and memory loss after tooth extraction 2 weeks before admission. Contrast computed tomography of the brain demonstrated a contrast rim-enhancing lesion over the left frontal lobe. With a history of recent dental procedure, long-term immunosuppressive therapy and computed tomography findings, cerebral abscess was highly suspected. Emergency operation was performed. Histopathology showed post-transplantation primary central nervous system lymphoma, with cells positive for B-cell marker CD20. Immunosuppressant was stopped and she was treated with radiotherapy and rituximab (anti-CD20 monoclonal antibody). She remained disease-free at 16 months. Post-transplantation primary central nervous system lymphoma is rare with variable presentation and radiological features. We believe rituximab may have a role in the treatment of such lymphomas. PMID:25488034

  11. Drug therapy reviews: antirheumatic agents.

    PubMed

    Evens, R P

    1979-05-01

    The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. PMID:377958

  12. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    PubMed Central

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  13. Polysaccharide from Lentinus edodes Inhibits the Immunosuppressive Function of Myeloid-Derived Suppressor Cells

    PubMed Central

    Liu, Xiaoman; Li, Xiao; Tang, Jian; Ma, Chungwah; Xu, Xiaofei; Shao, Haitao; Hou, Baidong; Wang, Hui; Qin, Zhihai

    2012-01-01

    Reversing the function of immune suppressor cells may improve the efficacy of cancer therapy. Here, we have isolated a novel polysaccharide MPSSS (577.2 Kd) from Lentinus edodes and examined its effects on differentiation and function of myeloid-derived suppressor cells (MDSCs). MPSSS is composed of glucose (75.0%), galactose (11.7%), mannose (7.8%), and xylose (0.4%). In vivo, it inhibits the growth of McgR32 tumor cells, which is correlated with a reduced percentage of MDSCs in peripheral blood. In vitro, it induces both morphological and biophysical changes in MDSCs. Importantly, MPSSS up-regulates MHC II and F4/80 expression on MDSCs, and reverses their inhibition effect on CD4+ T cells in a dose-dependent manner. The mechanism study shows that MPSSS may stimulate MDSCs through a MyD88 dependent NF-κB signaling pathway. Together, we demonstrated for the first time that MPSSS stimulates the differentiation of MDSCs and reverses its immunosuppressive functions, shedding new light on developing novel anti-cancer strategies by targeting MDSCs. PMID:23272159

  14. Ureaplasma septic arthritis in an immunosuppressed patient with juvenile idiopathic arthritis.

    PubMed

    George, Michael David; Cardenas, Ana Maria; Birnbaum, Belinda K; Gluckman, Stephen J

    2015-06-01

    Mycoplasmas, including Ureaplasma and Mycoplasma species, are uncommon but important causes of septic arthritis, especially affecting immunosuppressed patients. Many of the reported cases have been associated with congenital immunodeficiency disorders, especially hypogammaglobulinemia. Mycoplasmas are difficult to grow in the laboratory, and these infections may be underdiagnosed using culture techniques. We report a case of a 21-year-old woman with juvenile idiopathic arthritis and hip arthroplasties treated with rituximab and adalimumab who developed urogenital infections and soft tissue abscesses followed by knee arthritis with negative routine cultures. Ureaplasma species was identified from synovial fluid on 2 separate occasions using a broad-range 16S ribosomal RNA gene polymerase chain reaction. Azithromycin led to rapid improvement in symptoms, but after completion of therapy, involvement of the hip prosthesis became apparent, and again, 16S rRNA gene polymerase chain reaction was positive for Ureaplasma species. The literature is reviewed with a discussion of risk factors for Mycoplasma septic arthritis, clinical presentation, methods of diagnosis, and treatment. PMID:26010188

  15. Daily Associations among Anger Experience and Intimate Partner Aggression within Aggressive and Nonaggressive Community Couples

    PubMed Central

    Crane, Cory A.; Testa, Maria

    2014-01-01

    Anger is an empirically established precipitant to aggressive responding toward intimate partners. The current investigation examined the effects of anger, as experienced by both partners, as well as gender and previous aggression, on in vivo intimate partner aggression using a prospective daily diary methodology. Participants (N = 118 couples) individually provided 56 consecutive, daily reports of affective experience and partner aggression. Multilevel models were estimated using the Actor Partner Interdependence Model framework to analyze the daily associations between anger and partner aggression perpetration among male and female participants as moderated by aggression history. Results revealed that both Actor and Partner anger were generally associated with subsequently reported daily conflict. Further, increases in daily Partner anger were associated with corresponding increases in partner aggression among females who reported high anger and males, regardless of their own anger experience. Increases in Actor anger were associated with increases in daily partner aggression only among previously aggressive females. Previously aggressive males and females consistently reported greater perpetration than their nonaggressive counterparts on days of high Actor anger experience. Results emphasize the importance of both Actor and Partner factors in partner aggression and suggest that female anger may be a stronger predictor of both female-to-male and male-to-female partner aggression than male anger, when measured at the daily level. PMID:24866529

  16. Media depictions of physical and relational aggression: connections with aggression in young adults' romantic relationships.

    PubMed

    Coyne, Sarah M; Nelson, David A; Graham-Kevan, Nicola; Tew, Emily; Meng, K Nathan; Olsen, Joseph A

    2011-01-01

    Various studies have found that viewing physical or relational aggression in the media can impact subsequent engagement in aggressive behavior. However, this has rarely been examined in the context of relationships. Accordingly, the aim of this study was to examine the connection between viewing various types of aggression in the media and perpetration of aggression against a romantic partner. A total of 369 young adults completed a variety of questionnaires asking for their perpetration of various forms of relationship aggression. Participants' exposure to both physical and relational aggression in the media was also assessed. As a whole, we found a relationship between viewing aggression in the media and perpetration of aggression; however, this depended on the sex of the participant and the type of aggression measured. Specifically, exposure to physical violence in the media was related to engagement in physical aggression against their partner only for men. However, exposure to relational aggression in the media was related to romantic relational aggression for both men and women. PMID:21046605

  17. Competitive Aggression without Interaction: Effects of Competitive versus Cooperative Instructions on Aggressive Behavior in Video Games.

    ERIC Educational Resources Information Center

    Anderson, Craig A.; Morrow, Melissa

    1995-01-01

    Extended and tested Deutsch's theory of competition effects. Predicted that people view competitive situations as inherently more aggressive than cooperative ones. Predicted that leading people to think of an aggressive situation in competitive terms would increase aggressive behavior. Increase of kill ratio occurred in absence of changes in…

  18. Predicting Aggressive Behavior in Children with the Help of Measures of Implicit and Explicit Aggression

    ERIC Educational Resources Information Center

    Grumm, Mandy; Hein, Sascha; Fingerle, Michael

    2011-01-01

    Aggressive behavior between children in schools is a topic that receives much interest as violence and aggressive behavior cause many maladaptive social outcomes in the school setting. In the current study the Implicit Association Test (IAT) was adapted as a measure of children's implicit aggression, by assessing the association of the self…

  19. The Relationship of Aggression and Bullying to Social Preference: Differences in Gender and Types of Aggression

    ERIC Educational Resources Information Center

    Lee, Eunju

    2009-01-01

    With 338 fifth-grade students as subjects, this study found the variations in the relation between school bullying and social preference as a function of gender and types of aggressive behavior utilized. Aggressive boys were likely to be rejected by peers, whereas aggressive girls were both rejected and accepted by peers. Children nominated…

  20. Relational and Overt Aggression in Urban India: Associations with Peer Relations and Best Friends' Aggression

    ERIC Educational Resources Information Center

    Bowker, Julie C.; Ostrov, Jamie M.; Raja, Radhi

    2012-01-01

    This study explored the associations between relational and overt aggression and social status, and tested whether the peer correlates of aggression vary as a function of best friends' aggression during early adolescence in urban India. One hundred and ninety-four young adolescents from primarily middle-to-upper-class families in Surat, India…