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

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

2014-04-17

Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

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

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

2015-12-01

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

[Correlation of SNP of IL-2-330T/G Gene with Genetic Susceptibility and Efficacy of Immunosuppressive Therapy in Patients with Aplastic Anemia].

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Zeng, Qiang; Chang, Hong

2016-10-01

To investigate the correlation of single nucleotide polymorphism (SNP) of Interleukin-2(IL-2)-330T/G with genetic susceptibility and the efficacy of immunosuppressive therapy in patients with aplastic anemia. The peripheral blood samples from 103 patients with aplastic anemia in our hospital were collected. Out of 103 patients 46 received immuosuppressive therapy and were observed for 4 months, and 100 healthy adults were selected as control. The electrophoresis and DNA sequence were performed. The polymerase chain reaction(PCR) was used to amplify the polymorphic gene segment of IL-2 -330T/G from 103 aplastic anemia patients and 100 healthy adults. The frequencis of IL-2-330 GG genotype and G allele were a little higher in patients with aplastic anemia than that in the healthy adults(12.6% vs 12.0%, P>0.05; 27.7% vs 33.5%, P>0.05), but not statistically significant(P>0.05); in the 103 patients with aplastic anemia, 46 received immunosuppressive therapy, whereas 29 patients showed response, no significant difference was found between the responders and non-responders in the IL-2-330 GG genotype and G allele (31.0% vs 48.3%, P>0.05; 64.8% vs 61.8%, P>0.05). IL-2 -330T/G gene polymorphism may not correlate with the susceptibility of aplastic anemia or the efficacy of immunosuppressive therapy.

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

Directory of Open Access Journals (Sweden)

Poongodi Lakshmi Santhana Kumaraswamy

2016-01-01

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

Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.

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García-Barchino, Maria J; Sarasquete, Maria E; Panizo, Carlos; Morscio, Julie; Martinez, Antonio; Alcoceba, Miguel; Fresquet, Vicente; Gonzalez-Farre, Blanca; Paiva, Bruno; Young, Ken H; Robles, Eloy F; Roa, Sergio; Celay, Jon; Larrayoz, Marta; Rossi, Davide; Gaidano, Gianluca; Montes-Moreno, Santiago; Piris, Miguel A; Balanzategui, Ana; Jimenez, Cristina; Rodriguez, Idoia; Calasanz, Maria J; Larrayoz, Maria J; Segura, Victor; Garcia-Muñoz, Ricardo; Rabasa, Maria P; Yi, Shuhua; Li, Jianyong; Zhang, Mingzhi; Xu-Monette, Zijun Y; Puig-Moron, Noemi; Orfao, Alberto; Böttcher, Sebastian; Hernandez-Rivas, Jesus M; Miguel, Jesus San; Prosper, Felipe; Tousseyn, Thomas; Sagaert, Xavier; Gonzalez, Marcos; Martinez-Climent, Jose A

2018-05-01

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological

Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

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Seto, Wai-Kay

2015-01-01

Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negati...

Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide.

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Kanakry, Christopher G; Bolaños-Meade, Javier; Kasamon, Yvette L; Zahurak, Marianna; Durakovic, Nadira; Furlong, Terry; Mielcarek, Marco; Medeot, Marta; Gojo, Ivana; Smith, B Douglas; Kanakry, Jennifer A; Borrello, Ivan M; Brodsky, Robert A; Gladstone, Douglas E; Huff, Carol Ann; Matsui, William H; Swinnen, Lode J; Cooke, Kenneth R; Ambinder, Richard F; Fuchs, Ephraim J; de Lima, Marcos J; Andersson, Borje S; Varadhan, Ravi; O'Donnell, Paul V; Jones, Richard J; Luznik, Leo

2017-03-09

The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression. However, patients who develop GVHD require supplemental treatment. We assessed the longitudinal requirement for immunosuppressive therapy in 339 patients treated with this transplantation platform: 247 receiving busulfan/cyclophosphamide (BuCy) conditioning (data collected retrospectively) and 92 receiving busulfan/fludarabine (BuFlu) conditioning (data collected prospectively). Approximately 50% of MRD patients and 30% of MUD patients never required immunosuppression beyond PTCy. In patients requiring further immunosuppression, typically only 1 to 2 agents were required, and the median durations of systemic pharmacologic immunosuppression for the BuCy MRD, BuFlu MRD, BuCy MUD, and BuFlu MUD groups all were 4.5 to 5 months. For these 4 groups, 1-year probabilities of being alive and off all systemic immunosuppression were 61%, 53%, 53%, and 51% and 3-year probabilities were 53%, 48%, 49%, and 56%, respectively. These data suggest that PTCy minimizes the global immunosuppressive burden experienced by patients undergoing HLA-matched alloBMT.

Knowledge-based immunosuppressive therapy for kidney transplant patients--from theoretical model to clinical integration.

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Seeling, Walter; Plischke, Max; de Bruin, Jeroen S; Schuh, Christian

2015-01-01

Immunosuppressive therapy is a risky necessity after a patient received a kidney transplant. To reduce risks, a knowledge-based system was developed that determines the right dosage of the immunosuppresive agent Tacrolimus. A theoretical model, to classify medication blood levels as well as medication adaptions, was created using data from almost 500 patients, and over 13.000 examinations. This model was then translated into an Arden Syntax knowledge base, and integrated directly into the hospital information system of the Vienna General Hospital. In this paper we give an overview of the construction and integration of such a system.

Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

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Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan

2014-05-01

To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Varicella-zoster virus immunity in dermatological patients on systemic immunosuppressant treatment.

LENUS (Irish Health Repository)

Hackett, C B

2012-02-01

BACKGROUND: Primary varicella infection is caused by varicella-zoster virus (VZV). It is a common childhood infection, which is usually benign but can occasionally cause morbidity and mortality. In immunosuppressed adults, atypical presentation and disseminated disease can occur with significant morbidity and mortality. A VZV vaccine is available. OBJECTIVES: This study was designed to measure the prevalence of immunity to VZV and to determine the predictive value of a self-reported history of varicella infection in a population of dermatological patients receiving systemic immunosuppressant therapy. We sought to assess the need for routine serological testing for varicella-zoster immunity in this cohort. METHODS: Serological testing for VZV immunity was done on 228 patients receiving systemic immunosuppressive treatment for a dermatological condition. Information regarding a history of previous primary VZV infection was obtained from each patient. RESULTS: Two hundred and twenty-eight patients had VZV serology performed. The mean age of the patients was 49.6 years. The prevalence of VZV seropositivity in this cohort was 98.7%. One hundred and two patients (44.7%) reported having a definite history of primary VZV. The sensitivity of a self-reported history of VZV infection was 45.3% with a specificity of 100%. The positive and negative predictive values of a self-reported history of VZV for serologically confirmed immunity were 100% and 2.3%, respectively. CONCLUSIONS: The prevalence of VZV IgG antibodies in our cohort of Irish dermatology patients receiving immunosuppressive therapy is 98.7%. A recalled history of varicella infection is a good predictor of serological immunity. This study has shown that there are VZV-susceptible individuals within our cohort. These patients did not have a clear history of previous infection. We recommend serological testing of patients without a clear history of infection prior to the commencement of immunosuppressive therapy and

Immunosuppression following radiation therapy for carcinoma of the nasopharynx

International Nuclear Information System (INIS)

Wara, W.M.; Phillips, T.L.; Wara, D.W.; Ammann, A.J.; Smith, V.

1975-01-01

Eleven patients treated for nasopharyngeal carcinoma with standard radiation therapy were found to have depressed cell mediated immunity. Post-treatment their total lymphocyte count was decreased by 60 percent. Eight of 11 patients had depressed T-cell rosettes, and 9 of 10 had abnormal lymphocyte response to PHA. Immunosuppression was probably related to irradiation of large blood volumes, irradiation of the thymus, and malnutrition. (U.S.)

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

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

2016-03-01

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

Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression

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MCCANN, SHAUN

2002-01-01

PUBLISHED Background: Aplastic anemia may develop during pregnancy and sometimes improves spontaneously after delivery. The effects of pregnancy on aplastic anemia after immunosuppressive treatment and of aplastic anemia on the outcome of pregnancy have not been described. Objective: To determine the outcome of pregnancy and the disease course among women with aplastic anemia who received immunosuppressive therapy. Design: Retrospective multicenter study. Setting: Twelve cen...

The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious uveitis in childhood.

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Little, Jessica A; Sen, Ethan S; Strike, Helen; Hinchcliffe, Annie; Guly, Catherine M; Lee, Richard W J; Dick, Andrew D; Ramanan, Athimalaipet V

2014-01-01

To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY). In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

Association of time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected bacteria of patients after solid organ transplantation.

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Schmalz, G; Berisha, L; Wendorff, H; Widmer, F; Marcinkowski, A; Teschler, H; Sommerwerck, U; Haak, R; Kollmar, O; Ziebolz, D

2018-05-01

Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cyclosporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs. combination). Periodontal probing depth (PPD) and clinical attachment loss (CAL) were assessed. Periodontal disease severity was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were investigated for eleven selected potentially periodontal pathogenic bacteria using polymerasechainreaction. The mean PPD and CAL as well as prevalence of Treponema denticola and Capnocytophaga species was shown to be different but heterogeneous depending on time under immunosuppression (pperiodontal condition compared to patients without Cyclosporine (pperiodontal and microbiological parameters of patients after SOT. Patients under Cyclosporine medication should receive increased attention. Differences in subgingival biofilm, but not in clinical parameters were found for Glucocorticoids, Mycophenolate and combination therapy, making the clinical relevance of this finding unclear.

Efficacy of interventions for adherence to the immunosuppressive therapy in kidney transplant recipients: a meta-analysis and systematic review.

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Zhu, Yichen; Zhou, Yifan; Zhang, Lei; Zhang, Jian; Lin, Jun

2017-10-01

Immunosuppressive treatment regimens are complex and require ongoing self-management. Medication adherence can be difficult to achieve for several reasons. The current meta-analysis and systematic review investigated whether adherence interventions improved immunosuppressive treatment adherence in kidney transplant recipients. Medline, Cochrane, EMBASE, and Google Scholar were searched until October 17, 2016 using the following search terms: kidney transplantation, compliance, adherence, and immunosuppressive therapy. Randomized controlled trials and two-arm prospective, retrospective, and cohort studies were included. The primary outcomes were adherence rate and adherence score. Eight studies were included with a total for 546 patients. Among participants receiving intervention, the adherence rate was significantly higher than the control group (pooled OR=2.366, 95% CI 1.222 to 4.578, p=0.011). Participants in the intervention group had greater adherence scores than those in the control group (pooled standardized difference in means =1.706, 95% CI 0.346 to 3.065, p=0.014). Sensitivity analysis indicated that findings for adherence rate were robust. However, for adherence score, the significance of the association disappeared after removing one of the studies indicating the findings may have been overly influenced by this one study. Intervention programs designed to increase immunosuppressive adherence in patients with kidney transplant improve treatment adherence. Copyright © 2017 American Federation for Medical Research.

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

LENUS (Irish Health Repository)

Gabardi, Steven

2011-09-01

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

Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy

Institute of Scientific and Technical Information of China (English)

Kohtaro Ooka; Joseph K.Lim

2016-01-01

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

Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

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Nadia E. Aikawa

Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

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

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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. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation.

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Martin, Spencer T; Tichy, Eric M; Gabardi, Steven

2011-04-01

In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long-term use in renal transplant recipients. The costimulatory pathway (signal 2) of T-cell activation and proliferation is produced by stimulation of the T-cell surface marker, CD28, and is essential to the immune system's cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7-1 (CD80) and B7-2 (CD86) ligands present on antigen-presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living- and deceased-donor renal transplants, as well as in patients receiving kidneys transplanted from extended-criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy-proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin-based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein-Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long-term risks of belatacept are needed to better define its role as

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

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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 (Paplastic anemia. PMID:24816243

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

Science.gov (United States)

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

Immunosuppressive strategies and management

Institute of Scientific and Technical Information of China (English)

Shi-hui PAN

2008-01-01

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

Nanoparticles and direct immunosuppression

Science.gov (United States)

Ngobili, Terrika A

2016-01-01

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

Candidal carriage predicts candidiasis during topical immunosuppressive therapy: a preliminary retrospective cohort study.

Science.gov (United States)

Tejani, Sara; Sultan, Ahmed; Stojanov, Ivan; Woo, Sook-Bin

2016-10-01

To determine (1) the prevalence of candidal carriage in patients with oral mucosal disease to be treated with topical immunosuppressive therapy, and (2) the incidence of oral candidiasis among carriers and noncarriers after initiation of therapy to assess any correlation between carriage and the development of candidiasis. Records of patients who underwent swab cultures for Candida between January 2009 and October 2014 at the Brigham and Women's Hospital in Boston, Massachusetts, were retrospectively reviewed. The prevalence of candidal carriage and incidence of candidiasis were determined by using descriptive statistics. Of 99 evaluable patients, 20 (20.2%) were Candida positive and 79 (79.8%) were Candida negative. Of 44 patients with follow-up, 7 (15.9%) were Candida positive and 37 (84.1%) were Candida negative; five (11.4%) developed candidiasis. Four of seven (57.1%) Candida-positive patients developed candidiasis, whereas only one of 37 (2.7%) Candida-negative patients developed candidiasis (P = .0012). The overall prevalence of candidal carriage was low (20.2%), and there was a significant difference in the incidence of candidiasis between carriers and noncarriers (P = .0012) after topical immunosuppressive therapy. Therefore, patients who are candidal carriers should be monitored closely for the development of secondary candidiasis and may be candidates for prophylactic antifungal therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

Energy Technology Data Exchange (ETDEWEB)

Sonoda, Kazuhiko (Yamato Seiwa Hospital, Kanagawa (Japan)); Rapaport, F.T.

1992-12-01

With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author).

Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

International Nuclear Information System (INIS)

Sonoda, Kazuhiko; Rapaport, F.T.

1992-01-01

With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author)

Pancreatic islet allograft in spleen with immunosuppression with cyclosporine. Experimental model in dogs.

Science.gov (United States)

Waisberg, Jaques; Neff, Charles Benjamin; Waisberg, Daniel Reis; Germini, Demetrius; Gonçalves, José Eduardo; Zanotto, Arnaldo; Speranzini, Manlio Basilio

2011-01-01

To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. In the animals with immunosuppression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

The clinical value of immunosuppression in Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

International Nuclear Information System (INIS)

Chen Yue; Qiu Ling; Zhang Chunying; Long Shuiqing; Gan Xilun

2001-01-01

Objective: The chief clinical characteristics of Graves disease are hyperthyroidism and ophthalmopathy. To assess the values of using immunosuppression in Graves ophthalmopathy. Method: 415 patients with Graves hyperthyroidism were studied. They were randomly assigned to receive radioiodine, methimazole from 1.5 to 2 years, radioiodine followed by a 3-month course of prednisone. The changes in thyroid function and progression of ophthalmopathy were evaluated. Results: Among the 138 patients treated with radioiodine, 19 patients had new or worsening ophthalmopathy; 117 had no changes in their eyes; 2 patients had improvement in their eye disease. Among the 138 patients treated with methimazole, 3 patients had new or worsening ophthalmopathy; 133 had no changes in their eyes; 2 patients had improvement in their eye disease. Among the 139 patients treated with radioiodine and prednisone, no patient had new or worsening ophthalmopathy; 107 had no changes in their eyes; 32 patients had improvement in their eye disease. The frequency of improvement of ophthalmopathy was significantly higher in the radioiodine-prednisone group than in either the radioiodine group or the methimazole group (P<0.001 for both comparisons). Conclusions: The administration of prednisone after radioiodine therapy was associated with improvement of ophthalmopathy. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone

Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.

Science.gov (United States)

Samsel, R; Chmura, A; Włodarczyk, Z; Wyzgał, J; Cieciura, T; Lagiewska, B; Pliszczyński, J; Korczak, G; Lazowski, T; Paczek, L; Wałaszewski, J; Lao, M; Rowiński, W

1999-01-01

Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.

New Immunosuppressive Therapies in Uveitis Treatment

Directory of Open Access Journals (Sweden)

Salvador Mérida

2015-08-01

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

New Immunosuppressive Therapies in Uveitis Treatment

Science.gov (United States)

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

Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

Energy Technology Data Exchange (ETDEWEB)

Galvao, M.M.; Ianhez, L.E.; Sabbaga, E. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

1982-02-01

The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic /sup 131/I as a pre-transplantation immunosuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunosuppressive therapy. Significant differences were observed between the two groups regarding such factors as incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunosuppressive action, its administration being advised for receptors of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel.

Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

Science.gov (United States)

Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

2015-05-01

safe and was well tolerated. Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Foroutan N

2013-10-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

Science.gov (United States)

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse

Cutaneous Alternaria infectoria infection in a dog in association with therapeutic immunosuppression for the management of immune-mediated haemolytic anaemia

NARCIS (Netherlands)

Dedola, C.; Stuart, A.P.G.; Ridyard, A.E.; Else, R.W.; Van den Broek, T.; Choi, J.S.; de Hoog, G.S.; Thoday, K.L.

2010-01-01

A 4-year-old, ovariohysterectomized, English springer spaniel on immunosuppressive therapy was re-examined for the review of its immune-mediated haemolytic anaemia and the recent development of skin lesions. For the 3 months since hospital discharge, the dog had been receiving 1.3 mg/kg prednisolone

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

Science.gov (United States)

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

2014-01-01

A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. © 2014 Wiley Periodicals, Inc.

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

Directory of Open Access Journals (Sweden)

Yuan Cao

2015-01-01

Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

Risk factors for death in HIV-infected adult African patients receiving anti-retroviral therapy.

Science.gov (United States)

Siika, A M; Wools-Kaloustian, K; Mwangi, A W; Kimaiyo, S N; Diero, L O; Ayuo, P O; Owino-Ong'or, W D; Sidle, J E; Einterz, R M; Yiannoutsos, C T; Musick, B; Tierney, W M

2010-11-01

To determine risk factors for death in HIV-infected African patients on anti-retroviral therapy (ART). Retrospective Case-control study. The MOH-USAID-AMPATH Partnership ambulatory HIV-care clinics in western Kenya. Between November 2001 and December 2005 demographic, clinical and laboratory data from 527 deceased and 1054 living patients receiving ART were compared to determine independent risk factors for death. Median age at ART initiation was 38 versus 36 years for the deceased and living patients respectively (p100/mm3 (HR=1.553. 95% CI (1.156, 2.087), p<0.003). Patients attending rural clinics had threefold higher risk of dying compared to patients attending clinic at a tertiary referral hospital (p<0.0001). Two years after initiating treatment fifty percent of non-adherent patients were alive compared to 75% of adherent patients. Male gender, WHO Stage and haemoglobin level <10 grams% were associated with time to death while age, marital status, educational level, employment status and weight were not. Profoundly immunosuppressed patients were more likely to die early in the course of treatment. Also, patients receiving care in rural clinics were at greater risk of dying than those receiving care in the tertiary referral hospital.

Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

Science.gov (United States)

Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

2016-01-01

Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

Science.gov (United States)

Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

2002-01-01

To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

Ocular toxoplasmosis in immunosuppressed nonhuman primates

International Nuclear Information System (INIS)

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

1988-01-01

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

Ocular toxoplasmosis in immunosuppressed nonhuman primates

Energy Technology Data Exchange (ETDEWEB)

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

1988-06-01

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

Immunosuppressive drugs and fertility.

Science.gov (United States)

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

2015-10-21

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.

EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

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Niedobitek Gerald

2010-03-01

Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Immunosuppressive therapy for transplant-ineligible aplastic anemia patients.

Science.gov (United States)

Schrezenmeier, Hubert; Körper, Sixten; Höchsmann, Britta

2015-02-01

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

Function of external respiration in patients after kidney transplantation under conditions of immunosuppressive therapy.

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O. V. Kuryata

2018-04-01

Full Text Available The aim of our study was to evaluate the changes in the parameters of the function of external respiration in patients after kidney transplantation due to chronic kidney disease and to assess the relationship between the level of cyclosporin A and tacrolimus in the blood with FVD indices. The study included 37 patients after kidney transplantation. The first group included 27 patients who received cyclosporine at an average dose of 225 [175-350] mg/day under the immunosuppressive therapy regimen, the second group included 10 patients who received tacrolimus at an average dose of 8.25 [5.0-9.0] mg/day. A significant difference (p˂0.05 between the indicators of the VCmax (78 [71-90]% and 76.5 [72-78]%, FVC (93 [85-99]% and 95 [91-98]%, PEF (82 [64-94]% and 80 [69-84]%, MEF25-75 (75 [66-112]% and 82.5 [67-90]% was found in patients of the first and second groups relative to the FVD of the comparison group: VCmax (102.5 [98-113]%, FVC (107.5 [105.5-124]%, PEF (99.5 [95-102.5]%, MEF25-75 (98.5 [97.5-101.5]%. In both groups, a statistically significant negative correlation between the indicators of the VCmax, FVC and the level of cyclosporin A (R=-0.69, p<0.0001 and R=-0.4, p<0.037 in the blood in the first group and FVC and tacrolimus (R=-0.72, p<0.018 in the second group was found. A moderate decrease in the VCmax values in patients after kidney transplantation requires monitoring of the function of external respiration and managing such patients by nephrologists together with specialists in the pulmonological profile.

Efficiency of Photodynamic Therapy in the Treatment of Diffuse Facial Viral Warts in an Immunosuppressed Patient: Towards a Gold Standard

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M. Caucanas

2010-12-01

Full Text Available A 64-year-old man with a pulmonary transplant developed diffuse verrucae vulgares of the neck. After the failure of multiple cryotherapy treatments, 3 sessions of photodynamic therapy resulted in rapid therapeutic clinical success. This moderately painful and well-tolerated treatment is reproducible and can be very useful in treating papillomavirus infections in the immunosuppressed patient.

The influence of immunosuppressive treatment on the progression of Graves' disease after radioiodine

International Nuclear Information System (INIS)

Jurca, T.; Pirnat, E.; Hojker, S.; Avcin, J.

1994-01-01

Radioiodine therapy (RIT) for Graves' disease could produce a rise in autoimmune activity expressed as elevation of antibody against TSH receptors (TSI). In our retrospective study the influence of different immunosuppressive therapy on autoimmune activity was studied. Patients, treated with radioiodine or surgery for the first time, between January 1989 and March 1992 were included in the study, divided in the 5 groups (patients after thyroidectomy, and patients after RIT divided into groups according to treatment with different combinations of corticosteroids and cyclosporine A). Patients were examined and TT 4 , TT 3 TSH and TSI were collected before and 3, 6 and 9 months after treatment. There was no differences between groups before and according to the thyroid status the patients of all groups received antithyroid drugs or substitution therapy after the RIT or surgery. Immunosuppressive therapy was indicated because of Graves' ophthalmopathy. After surgery, the progressive fall of TSI and no relapses of the disease were stated. After first 3 months the situation was very similar in group of patients treated with cyclosporine A after RIT, later after the cessation of treatment, there were a slight elevation of TSI. In all other groups of patients after RIT there was a constant positive trend of TSI and the significant correlation was found between TSI before and after treatment. We conclude, that autoimmune response after RIT is a consequence of activity of T cells and therefore cyclosporine A could be taken in mind when we want to prevent it. Corticosteroids on the other hand had no such an effect. (author)

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

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Miller, James T; Collins, Curtis D; Stuckey, Linda J; Luan, Fu L; Englesbe, Michael J; Magee, John C; Park, Jeong M

2009-10-01

To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. Retrospective cohort study. Large academic medical center. Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, pTMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Management of HBV Infection During Immunosuppressive Treatment

OpenAIRE

Marzano, Alfredo

2009-01-01

The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), b) the treatment with antivirals (therapy) of active carriers, c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if...

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation.

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Heinemann, Falko M; Rebmann, Vera; Witzke, Oliver; Philipp, Thomas; Broelsch, Christoph E; Grosse-Wilde, Hans

2007-03-27

Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (PsCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.

Occupational Therapy and Physiotherapy in Acute Stroke: Do Rural Patients Receive Less Therapy?

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Josie Merchant

2016-01-01

Full Text Available Objective. To assess whether acute stroke patients in rural hospitals receive less occupational therapy and physiotherapy than those in metropolitan hospitals. Design. Retrospective case-control study of health data in patients ≤10 days after stroke. Setting. Occupational therapy and physiotherapy services in four rural hospitals and one metropolitan hospital. Participants. Acute stroke patients admitted in one health district. Main Outcome Measures. Frequency and duration of face-to-face and indirect therapy sessions. Results. Rural hospitals admitted 363 patients and metropolitan hospital admitted 378 patients. Mean age was 73 years. Those in rural hospitals received more face-to-face (p>0.0014 and indirect (p=0.001 occupational therapy when compared to those in the metropolitan hospital. Face-to-face sessions lasted longer (p=0.001. Patients admitted to the metropolitan hospital received more face-to-face (p>0.000 and indirect (p>0.000 physiotherapy when compared to those admitted to rural hospitals. Face-to-face sessions were shorter (p>0.000. Almost all were seen within 24 hours of referral. Conclusions. Acute stroke patients in Australian rural hospital may receive more occupational therapy and less physiotherapy than those in metropolitan hospitals. The dose of therapy was lower than recommended, and the referral process may unnecessarily delay the time from admission to a patient’s first therapy session.

Side Effects of Transplant Immunosuppressive Therapy in Post Renal Transplant Recipients, Mazandaran, Northern Iran

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Abazar Akbarzadeh Pasha

2017-04-01

Full Text Available Background Post-kidney transplant survival relies on patient adherence to the intake of immunosuppressive medication. This study was performed to investigate complications associated with immunosuppressive therapy in renal transplantation. Methods This cross-sectional study was conducted on 188 transplanted patients in Shahid Beheshti hospital of Babol in 2013. Check list and demographic questionnaire for data collecting were used. Then the data using were analyzed in SPSS.18 software by using chi-square test. Results A total of 188 transplanted patients, 115 (61.2% was male and mean age was 12.9 ± 42.9 years. 181 (96.3% of the subjects had at least one complication. The most common complication in 142 cases (75.5% was “excessive hair growth” and after this complication “increased blood sugar” had higher frequency and 119 (63.3% had this complication. Severe form of gingival overgrowth in women was significantly that more than men (22 (30.1, 14 (12.2, P = 0.004, and the other side effect was not significant difference between men and women or different age groups (P > 0.05 Conclusions Finding show that nearly all transplanted recipients suffered from one complication which need to recognize, control and treatment. It suggested that period visiting for early diagnosis and education to patient was recommend.

Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy.

LENUS (Irish Health Repository)

Lonergan, Roisin M

2012-02-01

Natalizumab therapy in multiple sclerosis has been associated with JC polyomavirus-induced progressive multifocal leucoencephalopathy. We hypothesized that natalizumab may also lead to reactivation of BK, a related human polyomavirus capable of causing morbidity in immunosuppressed groups. Patients with relapsing remitting multiple sclerosis treated with natalizumab were prospectively monitored for reactivation of BK virus in blood and urine samples, and for evidence of associated renal dysfunction. In this cohort, JC and BK DNA in blood and urine; cytomegalovirus (CMV) DNA in blood and urine; CD4 and CD8 T-lymphocyte counts and ratios in peripheral blood; and renal function were monitored at regular intervals. BK subtyping and noncoding control region sequencing was performed on samples demonstrating reactivation. Prior to commencement of natalizumab therapy, 3 of 36 patients with multiple sclerosis (8.3%) had BK viruria and BK reactivation occurred in 12 of 54 patients (22.2%). BK viruria was transient in 7, continuous in 2 patients, and persistent viruria was associated with transient viremia. Concomitant JC and CMV viral loads were undetectable. CD4:CD8 ratios fluctuated, but absolute CD4 counts did not fall below normal limits. In four of seven patients with BK virus reactivation, transient reductions in CD4 counts were observed at onset of BK viruria: these resolved in three of four patients on resuppression of BK replication. No renal dysfunction was observed in the cohort. BK virus reactivation can occur during natalizumab therapy; however, the significance in the absence of renal dysfunction is unclear. We propose regular monitoring for BK reactivation or at least for evidence of renal dysfunction in patients receiving natalizumab.

De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

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F. Friedersdorff

2010-04-01

Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

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Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

2016-06-02

To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under

Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings.

Science.gov (United States)

Kobayashi, Ryoji; Yabe, Hiromasa; Hara, Junichi; Morimoto, Akira; Tsuchida, Masahiro; Mugishima, Hideo; Ohara, Akira; Tsukimoto, Ichiro; Kato, Koji; Kigasawa, Hisato; Tabuchi, Ken; Nakahata, Tatsutoshi; Ohga, Shoichi; Kojima, Seiji

2006-12-01

The incidence of graft rejection was determined in 66 children with acquired aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related donor. Eleven of 65 evaluable patients experienced either early or late rejection. Multivariate analysis identified previous immunosuppressive therapy with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for graft rejection (relative risk: 16.6, P = 0.001). Patients who received ATG and CsA had a significantly lower probability of failure-free survival than those who did not (69.7 +/- 6.2% vs. 87.9 +/- 8.0%, P = 0.044). These results suggest that BMT should be instituted immediately in children with severe AA who have human leucocyte antigen-identical siblings.

Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

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Constantiner, Melissa; Rosenthal-Asher, Deborah; Tedla, Fasika; Salifu, Moro; Cukor, Judith; Wyka, Katarzyna; Hartono, Choli; Serur, David; de Boccardo, Graciela; Cukor, Daniel

2018-03-01

Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

[Therapy of intermediate uveitis].

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Doycheva, D; Deuter, C; Zierhut, M

2014-12-01

Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.

Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis.

Science.gov (United States)

Cui, Xin; Morales, Renee-Tyler Tan; Qian, Weiyi; Wang, Haoyu; Gagner, Jean-Pierre; Dolgalev, Igor; Placantonakis, Dimitris; Zagzag, David; Cimmino, Luisa; Snuderl, Matija; Lam, Raymond H W; Chen, Weiqiang

2018-04-01

altered ECM. Hence, we provide an interactive and controllable GBM tumor microenvironment and highlight the importance of macrophage-associated immunosuppression in GBM angiogenesis, paving a new direction of screening novel anti-angiogenic therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2017-01-01

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

A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

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Lorf Thomas

2010-04-01

Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

Awareness of memory impairment increases the adherence to immunosuppressants in kidney transplant recipients.

Science.gov (United States)

Cheng, C-Y; Lin, B Y-J; Chang, K-H; Shu, K-H; Wu, M-J

2012-04-01

Nonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients. All data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients. In summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

Relative reductions in soluble CD30 levels post-transplant predict acute graft function in islet allograft recipients receiving three different immunosuppression protocols.

Science.gov (United States)

Hire, Kelly; Hering, Bernhard; Bansal-Pakala, Pratima

2010-08-01

Despite advances in islet transplantation, challenges remain in monitoring for anti-islet immune responses. Soluble CD30 (sCD30) has been investigated as a predictor of acute rejection in kidney, lung, and heart transplantation as well as in a single study in human islet cell recipients. In this study, sCD30 levels were retrospectively assessed in 19 allograft recipients treated with three different immunosuppression induction therapies. Soluble CD30 levels were assessed at pre-transplant; early post-transplant (day 4-day 7); one-month post-transplant; and late post-transplant (day 90-day 120) and then correlated with eventual graft outcomes at 1-year follow-up. Results showed no correlation between mean serum sCD30 levels at any point in time pre- or post-transplant and graft function at 1-year follow-up. However, analysis demonstrated that mean sCD30 levels at day 28 or day 90-day 120 decreased from pre-transplant levels in recipients with long-term islet allograft function compared to recipients with partial or non-graft function (a decrease of 43.6+/-25.6% compared to 16.7+/-35.2%, psCD30 levels post-transplant overall. A larger reduction post-transplant correlated with full graft function. The results demonstrate that a relative reduction in sCD30 levels post-transplant may be applicable as a biomarker to monitor graft function in islet allograft recipients. Additionally, knowledge of the impact of various immunosuppression protocols on the timing and extent of changes in post-transplant sCD30 levels could aid in patient-specific tailoring of immunosuppression. Copyright © 2010 Elsevier B.V. All rights reserved.

Genetic factors for individual administration of immunosuppressants in organ transplantation

Institute of Scientific and Technical Information of China (English)

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

2006-01-01

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

Pneumonia in immunosuppressed patients; Pneumonien bei immunsupprimierten Patienten

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

2017-01-15

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

From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

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Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

2017-01-01

Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Low Risk of Pneumonia From Pneumocystis jirovecii Infection in Patients With Inflammatory Bowel Disease Receiving Immune Suppression.

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Cotter, Thomas G; Gathaiya, Nicola; Catania, Jelena; Loftus, Edward V; Tremaine, William J; Baddour, Larry M; Harmsen, W Scott; Zinsmeister, Alan R; Sandborn, William J; Limper, Andrew H; Pardi, Darrell S

2017-06-01

-years of exposure to triple therapy. Primary prophylaxis for PJP was prescribed to 37 patients, for a total of 24.9 patient-years of exposure. In a population-based cohort of patients with IBD treated with corticosteroids, immunosuppressants, and biologics, there were only 3 cases of PJP, despite the uncommon use of PJP prophylaxis. Routine administration of PJP prophylaxis in these patients may not be warranted, although it should be considered for high-risk groups, such as patients receiving triple therapy. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

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Way-Seah Lee

2017-10-01

Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth

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Han Zhipeng; Jing Yingying; Zhang Shanshan; Liu Yan; Shi Yufang; Wei Lixin

2012-01-01

Abstract Mesenchymal stem cells (MSCs) have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have ...

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

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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.

Generic maintenance immunosuppression in solid organ transplant recipients.

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Ensor, Christopher R; Trofe-Clark, Jennifer; Gabardi, Steven; McDevitt-Potter, Lisa M; Shullo, Michael A

2011-11-01

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

Menopause in women with chronic immunosuppressive treatment ? how to help those patients

OpenAIRE

Cyganek, Anna; Pietrzak, Bronis?awa; Wielgo?, Miros?aw; Grzechoci?ska, 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 ...

Immunosuppressive therapy in glomerular diseases: major accomplishment of Tadeusz Orłowski and his school.

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Smogorzewski, Mirosław J; Lao, Mieczysław; Gradowska, Liliana; Rowińska, Danuta; Rancewicz, Zofia

2009-05-01

Glomerulopathies are the third most common cause of end-stage renal failure. Immunosuppressive treatment of glomerulonephritis in a systematic way was introduced in Poland by Professor Tadeusz Orłowski in the early 1960s. The studies were conducted at the First Department of Medicine and at the Transplantation Institute of the Medical Academy in Warsaw in the years 1962-1988. This paper critically reviews the results of studies on the use of combined, triple-drug (prednisone/chlorambucil/azathioprine), immunosuppressive protocol in various pathological forms of glomerulopathies. We conclude that immunosuppressive protocols pioneered by Tadeusz Orłowski continue to be the backbone of the treatment of glomerulonephritis, especially the one with nephrotic syndrome, progressive impairment of kidney function and poor prognosis.

ATG-Fresenius S combined with cyclosporine a: an effective immunosuppressive therapy for children with aplastic anemia.

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Luo, Cheng-Juan; Gao, Yi-Jin; Tang, Jing-Yan; Zhu, Xiao-Hua; Xue, Hui-Liang; Lu, Feng-Juan; Pan, Ci; Jiang, Hua; Luo, Chang-Ying; Ye, Qi-Dong; Zhou, Min; Chen, Jing

2014-07-01

For the first time, we conducted a 2-center retrospective study to show the efficacy of antithymocyte globulin (ATG)-Fresenius S plus cyclosporine treatment of children with severe aplastic anemia. From March 1997 to May 2011, a total of 124 patients (median age, 7.5 y; range, 1.5 to 16 y) from 2 centers with acquired AA treated with an immunosuppressive therapy (IST) regimen, consisting of ATG-Fresenius S (5 mg/kg per day for 5 d) and cyclosporine, were enrolled. The response rate was 55.6%. The median time between IST and response was 6 (0.5 to 18) months. After a median follow-up time of 29 (6 to 153) months, the rates of relapse and clonal evolution were 3.2% and 0.8%, respectively. Overall, 17 patients (13.7%) died in this study: 14 resulted from sepsis, 1 resulted from intracranial hemorrhage, 1 occurred after hematopoietic stem cell transplantation, and 1 resulted from clonal disease progression. The 5-year overall survival rate for the entire cohort was 74.7%. IST responders had a better survival rate (100%) than nonresponders (70.7%). The use of ATG-Fresenius S plus cyclosporine as a first-line immunosuppressive treatment appeared to be effective for children with severe aplastic anemia in our study. ATG-Fresenius S could be another option in the treatment arsenal, especially in countries where the other ATG products are harder to acquire.

Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?

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Passweg, Jakob R.; Tichelli, André

2009-01-01

The combination of antithymocyte globulin of horse origin and cyclosporine A is the standard treatment for aplastic anemia in patients not eligible for bone marrow transplantation. In this perspective article, Drs. Passweg and Tichelli discuss the current immunosuppressive therapy of aplastic anemia. See related article on page 348.

Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation.

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Witkowska, Agnieszka; Strzalka-Mrozik, Barbara; Owczarek, Aleksander; Gola, Joanna; Mazurek, Urszula; Grzeszczak, Wladyslaw; Gumprecht, Janusz

2015-12-01

Chronic administration of immunosuppressants has been associated with long-term consequences, including a higher risk of neoplasm development. The processes regulating telomere function exert a major influence on human cancer biology. The present study aimed to assess the effect of immunosuppressive therapy on the expression of genes associated with telomere maintenance and protection in patients following renal transplantation. A total of 51 patients that had undergone kidney transplantation and 54 healthy controls were enrolled in the study. The 51 transplant patients received a three-drug immunosuppressive regimen consisting of cyclosporine A, prednisone and mycophenolate mofetil. In stage 1 of the study, the expression profiles of 123 transcripts, which represented 70 genes, were assessed in peripheral mononuclear blood cells using an oligonucleotide microarray technique in 8 transplant recipients and 4 healthy control subjects. Among the analyzed transcripts, the expression levels of 4 differed significantly between the studied groups; however, only the ACD (adrenocortical dysplasia homolog) gene, encoding the telomere-binding protein POT1-interacting protein 1 (TPP1), was sufficiently specific for telomere homeostasis. The expression of ACD was downregulated in transplant recipients (fold change, 2.11; P=0.006). In stage 2 of the study, reverse transcription-quantitative polymerase chain reaction analysis of ACD , DKC1 and hTERT mRNA was conducted for all transplant patients and control subjects. The results confirmed the downregulation of the ACD gene in patients that had received immunosuppressive therapy (P=0.002). The results of the present study indicate that the downregulation of ACD gene transcription, and thus TPP1 protein expression, may enhance the capacity for cell immortalization, despite normal levels of other key telomere maintenance factors, in patients undergoing immunosuppressive therapy. Furthermore, the results indicate that TPP1 has

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

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Richard Heyes

2016-01-01

Full Text Available This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs in promoting vascularized composite allotransplant (VCA tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.

Immunosuppressants

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... Brain Death HIV and Kidney Transplantation/Donation Incompatible Blood Types and Paired Exchange Programs Knowing Your Immunosuppressive (anti-rejection) Medications Organ and Tissue Donation The National Kidney ...

Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

International Nuclear Information System (INIS)

Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

1984-01-01

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

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

Directory of Open Access Journals (Sweden)

Anna Cyganek

2016-03-01

Full Text Available 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.

Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

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

2014-01-01

Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. 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. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

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

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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

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

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Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

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

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Cristina Costa

2012-03-01

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

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

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Emanuele D'Amico

Full Text Available 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?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.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.Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population.

CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

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Nicolas Espagnolle

2017-04-01

Full Text Available Summary: Mesenchymal stromal cells (MSCs sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therapy

[Evaluation of immunosuppressive treatment on homocystein levels in patients after kidney transplantation during a 2 year observation period].

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Aksamit, Dariusz; Janda, Katarzyna; Kuźniewski, Marek; Krzanowski, Marcin; Ignacak, Ewa; Betkowska-Prokop, Alina; Chowaniec, Eve; Sułowicz, Wladysław

2012-01-01

months after) did not differ significantly when compared to pts receiving immunosuppressive therapy CsA vs. Tac (p=0.18). Even though notable differences were observed in the drop in Hcy level (immunosuppressive treatment scheme CsA vs. Tac) in measurements before Ktx and 24 months post (respectively: 27% and 57.6%), no statistical significance was noted (p=0.13). Using the Mann-Whitneys' Test, no statistical significance was noted (p=0.13) when comparing differences in creatinine clearance between the group of pts receiving CsA and Tac 24 months after Ktx. Patients treated with Tac achieved a higher creatinine clearance by 16.5% when compared with those receiving CsA. No significant differences were observed between these two groups (p=0.65) when serum creatinine levels were evaluated. Incidence of DGF, as well as prescribed immunosuppressive therapy does not have an influence on remote Hey levels in pts after Ktx. Graft function seems to be the main predictor that influences Hcy levels after Ktx in this group of pts.

Candida albicans gastrointestinal colonization and invasion in the mouse: effect of antibacterial dosing, antifungal therapy and immunosuppression.

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Kinsman, O S; Pitblado, K

1989-12-01

Infant mice infected with Candida albicans by the oral-intragastric route became colonized in the gut and were persistently colonized into adulthood. Faecal levels of Candida were correlated with total gastrointestinal Candida and provided a useful means of detecting yeast overgrowth or elimination. Antibacterial agents promoting Candida overgrowth when given by the oral or parenteral route included ceftriaxone, augmentin and cefoperazone. Ceftizoxime had less effect. Ceftazidime and latamoxef produced raised levels only by the oral route. Gentamicin, vancomycin and metronidazole did not affect the Candida levels. Dosing with some antibacterials promoted an increase in gastrointestinal Candida and invasion to a greater extent than immunosuppression. Antifungal therapy to reduce gastrointestinal colonization was investigated using amphotericin B, nystatin, ketoconazole, intraconazole and fluconazole. Fluconazole was most effective at reducing faecal Candida.

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

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Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

2012-07-05

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

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Solène Coisy

2014-04-01

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

Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

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Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

2015-10-29

Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

EFFECTIVENESS AND SAFETY OF RECOMBINANT HUMAN GRANULOCYTIC COLONY-STIMULATING FACTOR IN TREATMENT OF GRANULOCYTOPENIA DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS

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E.I. Alexeeva

2010-01-01

Full Text Available Treatment of patients with severe clinical course of juvenile rheumatoid arthritis (JRA is difficult problem. During the last years genetically engineered biological drugs are used equally with traditional immunosuppressive agents in treatment of severe forms of juvenile arthritis. High effectiveness of these drugs can be accompanied with development of unfavorable effects, for example, febrile neutropenia. The article presents results of a study of effectiveness and safety of recombinant human granulocytic colony-stimulating factor — filgrastim (Leucostim — in treatment of granulocytopenia developed during immunosuppressive therapy in 16 patients with JRA. It was shown that administration of filgrastim arrests leucopenia in 100% of patients and granulocytopenia — in 93% of patients in 24 hours after first injection. High effectiveness of drug was combined with good tolerability and safety.Key words: children, treatment, granulocytopenia, filgrastim, juvenile rheumatoid arthritis.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:94-100

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation.

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

2015-11-01

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

Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

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James A. Bourgeois

2014-01-01

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

Cutaneous lymphoproliferative disorder complicating infectious mononucleosis in an immunosuppressed patient.

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Owen, Cindy England; Callen, Jeffrey P; Bahrami, Soon

2011-01-01

Infectious mononucleosis is the syndrome produced by primary infection with Epstein-Barr virus during adolescence or early adulthood. In immunosuppressed individuals, depressed T-cell function allows the Epstein-Barr virus-driven B-cell proliferation to continue unabated, potentially leading to a lymphoproliferative disorder. A 15-year-old girl with a history of ulcerative colitis treated with 6-mercaptopurine and mesalamine presented with the acute onset of a rapidly enlarging, ulcerative nodule on her left lower eyelid 4 weeks following recovery from infectious mononucleosis. The biopsy revealed an Epstein-Barr virus-positive lymphoproliferative disorder. Systemic disease was absent. Following discontinuation of 6-mercaptopurine, the patient was treated with two courses of intravenous cyclophosphamide. The lesion resolved completely and she remains disease free at 14 months following diagnosis. We report a solitary cutaneous lesion of an immunosuppression-related lymphoproliferative disorder (IR-LPD) occurring as a complication of infectious mononucleosis, and review the pathogenesis and reported cases of Epstein-Barr virus-related immunosuppression-related lymphoproliferative disorder arising in the setting of inflammatory bowel disease. It is important for dermatologists and dermatopathologists to be aware of the occurrence of IR-LPD in patients being treated for inflammatory conditions, including inflammatory bowel disease. Given the role of primary infection with Epstein-Barr virus in the development of IR-LPD, consideration may be given to assessing Epstein-Barr virus status prior to initiating immunosuppressive therapy in young patients. © 2010 Wiley Periodicals, Inc.

Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

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Hall, Victoria; Johnson, Douglas; Torresi, Joseph

2018-01-01

Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.

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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

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. 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. 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. 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.

Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

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Cuq, B; Blois, S L; Mathews, K A

2017-06-01

To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

Clinical aspects of immunosuppression in poultry.

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Hoerr, Frederic J

2010-03-01

Chickens, turkeys, and other poultry in a production environment can be exposed to stressors and infectious diseases that impair innate and acquired immunity, erode general health and welfare, and diminish genetic and nutritional potential for efficient production. Innate immunity can be affected by stressful physiologic events related to hatching and to environmental factors during the first week of life. Exposure to environmental ammonia, foodborne mycotoxins, and suboptimal nutrition can diminish innate immunity. Infectious bursal disease (IBD), chicken infectious anemia (CIA), and Marek's disease (MD) are major infectious diseases that increase susceptibility to viral, bacterial, and parasitic diseases and interfere with acquired vaccinal immunity. A shared feature is lymphocytolytic infection capable of suppressing both humoral and cell-mediated immune functions. Enteric viral infections can be accompanied by atrophic and depleted lymphoid organs, but the immunosuppressive features are modestly characterized. Some reoviruses cause atrophy of lymphoid organs and replicate in blood monocytes. Enteric parvoviruses of chickens and turkeys merit further study for immunosuppression. Hemorrhagic enteritis of turkeys has immunosuppressive features similar to IBD. Other virulent fowl adenoviruses have immunosuppressive capabilities. Newcastle disease can damage lymphoid tissues and macrophages. Avian pneumovirus infections impair the mucociliary functions of the upper respiratory tract and augment deeper bacterial infections. Recognition of immunosuppression involves detection of specific diseases using diagnostic tests such as serology, etiologic agent detection, and pathology. Broader measurements of immunosuppression by combined noninfectious and infectious causes have not found general application. Microarray technology to detect genetic expression of immunologic mediators and receptors offers potential advances but is currently at the developmental state. Control

Cancer immunotherapy by immunosuppression

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Prehn Liisa M

2010-12-01

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

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

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Mika, Adriana; Stepnowski, Piotr

2016-08-05

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Successful Immunosuppressive Therapy for Severe Infectious Mononucleosis in a Patient with Clonal Proliferation of EBV-infected CD8-positive Cells.

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Hosoi, Hiroki; Sonoki, Takashi; Murata, Shogo; Mushino, Toshiki; Kuriyama, Kodai; Nishikawa, Akinori; Hanaoka, Nobuyoshi; Ohshima, Koichi; Imadome, Ken-Ichi; Nakakuma, Hideki

2015-01-01

A 30-year-old woman was diagnosed with severe infectious mononucleosis (IM). The Epstein-Barr virus (EBV) had infected both CD19- and CD8-positive cells, and clonal proliferation of EBV-infected cells and T-cells was detected. Although we suspected malignant lymphoma, her condition improved following immunosuppressive therapy. A similar case was recently reported; therefore, this case is the second case of IM with EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells. Our results demonstrate that the clonal proliferation of EBV-infected cells is not always an indication for chemotherapy in the primary infection phase and that monitoring the EBV viral load is useful for therapeutic decision-making.

Antipsychotic Polypharmacy in a Treatment-Refractory Schizophrenia Population Receiving Adjunctive Treatment With Electroconvulsive Therapy

DEFF Research Database (Denmark)

Kristensen, Diana; Hageman, Ida; Bauer, Jeanett

2013-01-01

Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT).......Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT)....

Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

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Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

2015-01-01

Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

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

OpenAIRE

Denhaerynck, Kris

2006-01-01

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

Endogenous nocardial endophthalmitis in an immunosuppressed patient: A serious warning of an underlying life threatening and blinding disorder

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Hemant Trehan

2017-01-01

Conclusion: Ocular nocardiosis is a serious vision and life threatening disorder, particularly in patients on immunosuppressive therapy. A high index of suspicion is required for successful treatment.

Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

NARCIS (Netherlands)

Khanna, Reena; Bressler, Brian; Levesque, Barrett G.; Zou, Guangyong; Stitt, Larry W.; Greenberg, Gordon R.; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J.; Donner, Allan; Vandervoort, Margaret K.; Morris, Joan C.; Feagan, Brian G.; Anderson, Frank; Atkinson, Kenneth; Bacchus, Rahman; Berezny, Gary; Borthistle, Bruce; Buckley, Alan; Chiba, Naoki; Cockeram, Alan; Elkashab, Magdy; Fashir, Baroudi; Gray, James; Hemphill, Douglas; Hoare, Connie; Holland, Stephen; Hurowitz, Eric; Kaal, Nuri; Laflamme, Pierre; Borromee, Saint-Charles; Lau, Helena; McMullen, William; Memiche, Reshat; Menon, Krishna; Miller, D. Alexander; O'Hara, William; Oravec, Michael; Penner, Robert; Petrunia, Denis; Pluta, Henryk; Prabhu, Umesh; Prest, Marcia; Shaaban, Hani; Sheppard, Duane; Shulman, Scott

2015-01-01

Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of

Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy

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Hiroyuki Horiguchi

2018-04-01

Full Text Available Clinical and technological advances promoting early hemorrhage control and physiologic resuscitation as well as early diagnosis and optimal treatment of sepsis have significantly decreased in-hospital mortality for many critically ill patient populations. However, a substantial proportion of severe trauma and sepsis survivors will develop protracted organ dysfunction termed chronic critical illness (CCI, defined as ≥14 days requiring intensive care unit (ICU resources with ongoing organ dysfunction. A subset of CCI patients will develop the persistent inflammation, immunosuppression, and catabolism syndrome (PICS, and these individuals are predisposed to a poor quality of life and indolent death. We propose that CCI and PICS after trauma or sepsis are the result of an inappropriate bone marrow response characterized by the generation of dysfunctional myeloid populations at the expense of lympho- and erythropoiesis. This review describes similarities among CCI/PICS phenotypes in sepsis, cancer, and aging and reviews the role of aberrant myelopoiesis in the pathophysiology of CCI and PICS. In addition, we characterize pathogen recognition, the interface between innate and adaptive immune systems, and therapeutic approaches including immune modulators, gut microbiota support, and nutritional and exercise therapy. Finally, we discuss the future of diagnostic and prognostic approaches guided by machine and deep-learning models trained and validated on big data to identify patients for whom these approaches will yield the greatest benefits. A deeper understanding of the pathophysiology of CCI and PICS and continued investigation into novel therapies harbor the potential to improve the current dismal long-term outcomes for critically ill post-injury and post-infection patients.

Symptomatic burden of COPD for patients receiving dual or triple therapy

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Chen S

2018-04-01

Full Text Available Stephanie Chen,1 Mark Small,2 Leandro Lindner,3 Xiao Xu1,4 1Health Economics and Payer Analytics, AstraZeneca, Gaithersburg, MD, USA; 2Respiratory, Adelphi Real World, Bollington, UK; 3Global Payer Evidence and Pricing, AstraZeneca, Cambridge, UK; 4Global Payer Evidence and Pricing, AstraZeneca, Gaithersburg, MD, USA Background: COPD is associated with a large disease burden. The use of dual (two maintenance treatments and triple (combination of any three treatments therapy has shown efficacy for symptom relief; however, some patients with COPD remain symptomatic despite these therapies. This study assessed the scope and magnitude of the symptomatic burden for patients with COPD receiving dual or triple therapy. Patients and methods: Cross-sectional data from three Adelphi COPD surveys (2013–2016 conducted in the USA, Europe, Japan, and China were analyzed for patients with COPD and forced expiratory volume in 1 second ≤65% receiving dual or triple therapy for ≥3 months. Physicians completed clinical and disease characteristic forms for identified patients. Corresponding patients completed questionnaires that included validated survey instruments to assess adherence and symptom impact. Descriptive statistics are reported. Results: Our analysis included 690 patients (mean age 68.2 years; 73.3% male; 41.4% and 58.6% were receiving dual and triple therapy, respectively. Most patients had dyspnea with substantial disability (modified Medical Research Council dyspnea scale rating ≥2, 56.3%; large health status impairment from symptoms, COPD Assessment Test score >20, 64.4%. A large symptom burden was observed, even for patients highly adherent to treatment (Morisky Medication Adherence Scale 8, 30.3% [185/612], of whom 62.1% still had a COPD Assessment Test score >20. Sensitivity analyses of patients regardless of their forced expiratory volume in 1 second status and of those receiving treatment for >6 months both reported similar results

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

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

2016-01-01

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

Immunosuppressive drugs and fertility

OpenAIRE

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 ...

6-methylprednisolone does not impair anti-thymocyte globulin (ATG) immunosuppressive activity in non-human primates

NARCIS (Netherlands)

Preville, [No Value; Sick, E; Beauchard, S; Ossevoort, M; Tiollier, J; Revillard, JP; Jonker, Margreet

2001-01-01

Background: Induction treatments with anti-thymocyte globulin (ATG) in solid organ transplantation may enhance the efficacy of maintenance immunosuppressive therapy. Since ATG can trigger Fas (CD95) mediated T cell apoptosis, a process antagonized in vitro by corticosteroids, an important issue is

DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.

Science.gov (United States)

Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

2016-07-01

Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

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Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

2016-10-15

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

The Effects of Music Therapy on the Physiological Response of Asthmatic Children Receiving Inhalation Therapy.

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Roslita, Riau; Nurhaeni, Nani; Wanda, Dessie

The clinical manifestation of asthma in children can interfere with their daily activities. Music therapy may become one of the alternative approaches to making children feel comfortable during inhalation therapy. The aim of the study was to identify the effects of music therapy on the physiological response of asthmatic preschool and school-age children receiving inhalation therapy. This study used a quasi-experimental, nonequivalent control group with a pre-test-post-test design. The 44 respondents consisted of preschool and school-age children assigned to intervention and control groups. The results showed a significant difference in average oxygen saturation, heart rate, and respiratory rate between the control and intervention groups before and after intervention (p Music therapy can be used as a nursing intervention to improve the physiological response of children with breathing problems.

Prolonged extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome in a child affected by rituximab-resistant autoimmune hemolytic anemia: a case report

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Beretta Chiara

2009-04-01

Full Text Available Abstract Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our

Where Do Patients With Cancer in Iowa Receive Radiation Therapy?

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Ward, Marcia M.; Ullrich, Fred; Matthews, Kevin; Rushton, Gerard; Tracy, Roger; Goldstein, Michael A.; Bajorin, Dean F.; Kosty, Michael P.; Bruinooge, Suanna S.; Hanley, Amy; Jacobson, Geraldine M.; Lynch, Charles F.

2014-01-01

Purpose: Multiple studies have shown survival benefits in patients with cancer treated with radiation therapy, but access to treatment facilities has been found to limit its use. This study was undertaken to examine access issues in Iowa and determine a methodology for conducting a similar national analysis. Patients and Methods: All Iowa residents who received radiation therapy regardless of where they were diagnosed or treated were identified through the Iowa Cancer Registry (ICR). Radiation oncologists were identified through the Iowa Physician Information System (IPIS). Radiation facilities were identified through IPIS and classified using the Commission on Cancer accreditation standard. Results: Between 2004 and 2010, 113,885 invasive cancers in 106,603 patients, 28.5% of whom received radiation treatment, were entered in ICR. Mean and median travel times were 25.8 and 20.1 minutes, respectively, to the nearest facility but 42.4 and 29.1 minutes, respectively, to the patient's chosen treatment facility. Multivariable analysis predicting travel time showed significant relationships for disease site, age, residence location, and facility category. Residents of small and isolated rural towns traveled nearly 3× longer than urban residents to receive radiation therapy, as did patients using certain categories of facilities. Conclusion: Half of Iowa patients could reach their nearest facility in 20 minutes, but instead, they traveled 30 minutes on average to receive treatment. The findings identified certain groups of patients with cancer who chose more distant facilities. However, other groups of patients with cancer, namely those residing in rural areas, had less choice, and some had to travel considerably farther to radiation facilities than urban patients. PMID:24443730

Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis

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Sotsiou Florentia

2005-12-01

Full Text Available Abstract Background Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment. Methods Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA. TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange. Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. Results Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively. In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p 1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence

Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

DEFF Research Database (Denmark)

Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

2004-01-01

A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...... indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case...

Effects of immunosuppressive treatment on protein expression in rat kidney

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Kędzierska K

2014-09-01

were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2 and markers of distal renal tubular damage (heart fatty acid-binding protein compared to expression in the CMG group. The consequences of the reported changes in protein expression require further study. Keywords: Proteomics, drug effects, immunosuppression, rats

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

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Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

1990-10-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

International Nuclear Information System (INIS)

Easterling, K.J.; Trumble, T.E.

1990-01-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

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Sergey V. Tokalov

2010-01-01

Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

Immunomodulator, immunosuppression of radiation and immune reconstruction

International Nuclear Information System (INIS)

Mao Jianping; Fang Jing; Zhou Ying; Cui Yufang; Jiang Zhujun; Du Li; Ma Qiong

2010-01-01

There is a refined and complicated regulatory network between immune cells, and between immune cells and secretory factors. The immune system is kept in a homeostasis and equilibrium by positive activation and negative inhibition. In recent years, the mechanisms of immunosuppression in depth for successful allograft transplantation were studied, and many immunosuppressants and immunosuppressive drugs have been developed for clinical use. Most of them are targeting T cell receptors and three kinds of singnal pathways. The receptors of the immunosuppression were either found highly expressed in immune cells after irradiation. To relieve the suppression by regulating the receptors could help the immune reconstruction out of radiation damage. Many new immunoenhancers have been discovered to improve the immune system function for radiation by Toll-like receptors. The search for new immunoenhancers and agents for relieving immunosuppression is of great importance to immune construction for radiation sickness. (authors)

Assessment of readiness for clinical decision support to aid laboratory monitoring of immunosuppressive care at U.S. liver transplant centers.

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Jacobs, J; Weir, C; Evans, R S; Staes, C

2014-01-01

Following liver transplantation, patients require lifelong immunosuppressive care and monitoring. Computerized clinical decision support (CDS) has been shown to improve post-transplant immunosuppressive care processes and outcomes. The readiness of transplant information systems to implement computerized CDS to support post-transplant care is unknown. a) Describe the current clinical information system functionality and manual and automated processes for laboratory monitoring of immunosuppressive care, b) describe the use of guidelines that may be used to produce computable logic and the use of computerized alerts to support guideline adherence, and c) explore barriers to implementation of CDS in U.S. liver transplant centers. We developed a web-based survey using cognitive interviewing techniques. We surveyed 119 U.S. transplant programs that performed at least five liver transplantations per year during 2010-2012. Responses were summarized using descriptive analyses; barriers were identified using qualitative methods. Respondents from 80 programs (67% response rate) completed the survey. While 98% of programs reported having an electronic health record (EHR), all programs used paper-based manual processes to receive or track immunosuppressive laboratory results. Most programs (85%) reported that 30% or more of their patients used external laboratories for routine testing. Few programs (19%) received most external laboratory results as discrete data via electronic interfaces while most (80%) manually entered laboratory results into the EHR; less than half (42%) could integrate internal and external laboratory results. Nearly all programs had guidelines regarding pre-specified target ranges (92%) or testing schedules (97%) for managing immunosuppressive care. Few programs used computerized alerting to notify transplant coordinators of out-of-range (27%) or overdue laboratory results (20%). Use of EHRs is common, yet all liver transplant programs were largely

Renal Transplant Recipients: The Factors Related to Immunosuppressive Medication Adherence Based on the Health Belief Model.

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Kung, Pen-Chen; Yeh, Mei Chang; Lai, Ming-Kuen; Liu, Hsueh-Erh

2017-10-01

Kidney transplant failures are caused primarily by lack of adherence to immunosuppressive medication regimens by patients after transplantation. A number of studies have indicated that health-related beliefs are an effective predictor of health-related behavior. The aim of this study is to understand the influence of the personal characteristics and health-related beliefs of patients on adherence to treatment with immunosuppressive medication based on the Health Belief Model. This cross-sectional study distributed questionnaires to patients who had been recruited via purposive sampling at one medical center in Taipei. All of the potential participants had undergone kidney transplantation at least 6 months previously. The self-developed questionnaire collected data in three areas: personal characteristics, health-related beliefs regarding transplant rejection, and adherence to the immunosuppressive medication regimen. One hundred twenty-two valid questionnaires were received. The collected data were analyzed using descriptive statistics, independent t test, one-way analysis of variance, Pearson's correlation, and multiple regression. Participants who had received dialysis treatment or had experienced rejection perceived susceptibility to rejection more strongly than those who had not. Participants who had undergone transplantation in Taiwan, had experienced more drug-related symptoms, or had contracted severe to extremely severe infections in the past showed lower rates of adherence to treatment with immunosuppressive medication. Adherence to medication regimens correlated negatively with length of time since transplantation. Length of time since transplantation, drug-related symptoms, perceived susceptibility to rejection, and perceived benefits of treatment were identified as major predictors of adherence to immunosuppressive medication regimens. The results partially conformed to the concepts of the Health Belief Model. Perceived susceptibility to rejection and

Cost utility analysis of immunosuppressive regimens in adult renal transplant recipients in England and Wales

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Muduma G

2014-11-01

Full Text Available Gorden Muduma,1 Jane Shaw,2 Warren M Hart,3 Abayomi Odeyemi,3 Isaac Odeyemi21Astellas Pharma Europe Limited, Chertsey, UK; 2Astellas Pharma Limited, Chertsey, UK; 3EcoStat Consulting UK Limited, London, UKBackground: End-stage renal disease is the irreversible final stage of chronic kidney disease and is fatal when not managed by either transplantation or dialysis. Transplantation is generally preferred over dialysis. However, to prevent graft rejection or loss, lifelong immunosuppression is required. Tacrolimus is currently the cornerstone of post-transplantation immunosuppression. The study aim was to carry out an economic evaluation of immunosuppression, including more recent agents such as a once-daily prolonged-release formulation of tacrolimus (Advagraf™ and belatacept, relative to a twice-daily immediate-release formulation of tacrolimus (Prograf™.Methods: A model was constructed comprising six states: onset of biopsy-confirmed acute rejection, functioning graft with or without a biopsy-confirmed acute rejection, non-functioning graft (dialysis, re-transplantation, and death. Data on clinical effectiveness were derived from a systematic literature review and the model captured the effects of patient adherence to immunosuppressant therapy on graft survival using relative risk of graft survival and published data on adherence in patients using Advagraf and Prograf. In the base case, the time horizon was 25 years and one-way and probabilistic sensitivity analyses were conducted.Results: The analysis demonstrated that Prograf was cost-effective when compared with cyclosporin and belatacept and was more effective than sirolimus, but would not be considered cost-effective against sirolimus. The modeled improvement in the adherence profile of patients using Advagraf relative to Prograf resulted in both improved clinical outcomes and reduced costs. Conclusion: Prograf was more clinically effective than cyclosporin, belatacept, and sirolimus

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

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Muduma G

2016-01-01

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

Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.

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Akawatcharangura, P; Taechakraichana, N; Osiri, M

2016-04-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients. © The Author(s) 2015.

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

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

2016-08-29

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

Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression

International Nuclear Information System (INIS)

Blum, J.E.; de Silva, S.M.; Rachman, D.B.; Order, S.E.

1988-01-01

Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity

Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

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Gianluigi Zaza

Full Text Available The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined.We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group, and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group.A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05. Flagellar motor switch protein (fliNY and type IV pilus assembly protein pilM (pilM were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity.Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

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Zaza, Gianluigi; Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

2017-01-01

The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen

Science.gov (United States)

Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

2017-01-01

Background The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. Methods We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). Results A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Conclusions Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this

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

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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

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

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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.

Monitoring the patient off immunosuppression. Conceptual framework for a proposed tolerance assay study in liver transplant recipients.

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Thomson, A W; Mazariegos, G V; Reyes, J; Donnenberg, V S; Donnenberg, A D; Bentlejewski, C; Zahorchak, A F; O'Connell, P J; Fung, J J; Jankowska-Gan, E; Burlingham, W J; Heeger, P S; Zeevi, A

2001-10-27

The mission of the recently established Immune Tolerance Network includes the development of protocols for the induction of transplant tolerance in organ allograft recipients and the development of assays that correlate with and may be predictive of the tolerant state. The state of clinical organ transplant tolerance seems to already exist in a small minority of conventionally immunosuppressed liver and, more rarely, kidney transplant patients. Immunosuppressive drug therapy has been withdrawn from these patients for a variety of reasons, including protocolized weaning for a uniquely large group of liver patients at the University of Pittsburgh. In this study, we propose to evaluate the validity of a variety of in vitro immunologic and molecular biologic tests that may correlate with, and be predictive of, the state of organ transplant tolerance in stable liver patients off immunosuppression. Only peripheral blood will be available for the execution of these tests. Both adult and pediatric liver graft recipients will be studied, in comparison to appropriate controls. We shall examine circulating dendritic cell (DC) subsets [precursor (p) DC1 and p DC2] including cells of donor origin, and assess both the frequency and function of donor-reactive T cells by ELISPOT and by trans-vivo delayed-type hypersensitivity analysis in a surrogate murine model. Cytokine gene polymorphism and alloantibody titers will also be investigated. It is anticipated that the results obtained may provide physicians with a tolerance assay "profile" that may determine those patients from whom immunosuppressive therapy may be safely withdrawn.

Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women

DEFF Research Database (Denmark)

Roensbo, Mette T; Blaakær, Jan; Skov, Karin

2018-01-01

INTRODUCTION: Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed...... in 2014 had three cervical cytologies performed; one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas(®) HPV Test and CLART(®) HPV2 Test. RESULTS: Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high......-risk HPV was 15.0 (95% CI; 7.1-26.6) and the prevalence was higher among BMTR (29.4, CI; 10.3-56.0) than in RTR (9.3%, CI; 2.6-22.1) although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad with HPV 45 as the most common genotype (3.3%). The prevalences of high...

Generic immunosuppression in transplantation: current evidence and controversial issues.

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El Hajj, Sandra; Kim, Miae; Phillips, Karen; Gabardi, Steven

2015-05-01

The overall success of organ transplantation in the 21st century has been predicated, in part, on the use of newer, more potent, and selective immunosuppressive agents. However, the high cost of lifelong immunosuppression represents a financial burden for many patients. In the past 15 years, regulatory agencies in Europe and America have approved several generic immunosuppressants. One concern is whether the conversion between innovator and generic immunosuppressants will prove to be problematic. This manuscript aims to compare and contrast the bioequivalence requirements among regulatory authorities in the USA, Europe, and Canada, evaluate published studies of generic immunosuppressants in transplant recipients, summarize consensus statements made by transplant organizations and discuss how to engage patients in discussion regarding the choice between innovator and generic immunosuppressants.

Early Introduction of Everolimus Immunosuppressive Regimen in Liver Transplantation with Extra-Anatomic Aortoiliac-Hepatic Arterial Graft Anastomosis

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Emanuele Felli

2014-01-01

Full Text Available Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease, when no other medical treatment is possible. Despite high rates of 1- to 5-year survival, long-term adverse effects of immunosuppressant agents remain of major concern. Current research and clinical efforts are made to develop immunosuppressant agents that minimize adverse effects along with a low rate of graft rejection. Tailoring immunosuppressive therapy to individual patients by the use of proliferation signal inhibitors seems to be the best way to minimize toxicity and increase efficacy. Recently everolimus has been introduced in clinical practice; among its adverse effects an increased incidence of arterial graft thrombosis in renal transplants, vascular anastomosis leakage, impaired wound healing, and thrombotic microangiopathy have been reported. We present the case of a 54-year-old patient submitted to liver transplantation for end-stage liver disease treated by an extra-anatomic aortoiliac-hepatic arterial graft anastomosis and early postoperative introduction of everolimus for acute renal failure. Postoperative period was characterized by two abdominal collections and reactivation of cytomegalovirus infection that were treated by percutaneous drainage and antiviral therapy, respectively; the patient is well after 8-month followup with patency of the arterial conduit and no leakage.

Rat allotransplantation of epigastric microsurgical flaps: a study of rejection and the immunosuppressive effect of cyclosporin A

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Carramaschi Fábio R.

2000-01-01

Full Text Available The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1 Wistar Furth isogenic donors and receptors (control set; (2 Brown Norway donors and Wistar Furth receptors (rejection set; and (3 Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set. Cyclosporin A (10 mg/kg/d treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.

Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

DEFF Research Database (Denmark)

Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

2004-01-01

A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...... indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case...... of tuberculosis. We suggest that RD1 based tests are evaluated further in immunocompromised patients....

Immunosuppressive medication adherence in kidney transplant patients.

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Lalić, Jelena; Veličković-Radovanović, Radmila; Mitić, Branka; Paunović, Goran; Cvetković, Tatjana

2014-01-01

To assess the degree of immunosuppressive medication adherence in kidney transplant patients (KTPs) and to determine if there is a difference in the rate of adherence to tacrolimus (Tac), cyclosporine (CsA) and sirolimus (Sir). From a total of 63 KTPs treated at the Clinic of Nephrology, Clinical Centre Niš, Serbia, 60 participated in the study by responding to questionnaires. They were divided into the adherence group (n = 43) and the nonadherence group (n = 17) according to their degree of adherence which was measured using a validated survey form, the simplified medication adherence questionnaire. The KTP adherence to the different immunosuppressive regimens (Tac, CsA and Sir) was compared. Statistical analysis was performed using the Student t test. Adherence was observed in 43 (71.7%) patients, and only 17 (28.3%) did not follow the prescribed therapy. The estimated glomerular filtration rate was significantly lower in the nonadherence group (38.52 ± 18.22 ml/min) than in the adherence group (52.43 ± 16.91 ml/min, p adherers and the nonadherers (6.30 ± 2.06 vs. 5.0 ± 1.52 ng/ml, p adherence. Nonadherence was associated with worse graft function and a lower Tac level. Knowledge about the degree of adherence could help the early identification of nonadherent patients and the development of strategies to improve this. © 2014 S. Karger AG, Basel

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

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Shahin Gaini

2015-01-01

Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

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

DEFF Research Database (Denmark)

Gaini, Shahin

2015-01-01

A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

Chlorphenesin: an antigen-associated immunosuppressant.

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Whang, H Y; Neter, E

1970-07-01

Chlorphenesin (3-p-chlorophenoxy-1,2-propanediol), when injected intravenously together with either of two common bacterial antigens, inhibits the antibody response of the rabbit. The antigens studied are those common to Enterobacteriaceae and to gram-positive bacteria. The immunosuppression is contingent upon incubation of chlorphenesin and antigen in vitro prior to administration, since separate injection of antigen and inhibitor or of mixtures without prior incubation yields undiminished antibody response. Chlorphenesin, as shown by hemagglutination-inhibition tests, does not alter the antigenic determinants, because antibody neutralization occurs in the presence or absence of the drug. The immunosuppressive effect is reversible, since precipitation of chlorphenesin at 4 C substantially restores immunogenicity. Animals immunized with antigen-drug mixtures, which fail to respond with significant antibody production, nonetheless are immunologically primed. It is concluded that chlorphenesin represents another example of antigen-associated immunosuppressants.

Predicting dropout in adolescents receiving therapy for depression.

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O'Keeffe, Sally; Martin, Peter; Goodyer, Ian M; Wilkinson, Paul; Consortium, Impact; Midgley, Nick

2017-10-30

Therapy dropout is a common occurrence, especially in adolescence. This study investigated whether dropout could be predicted from a range of child, family, and treatment factors in a sample of adolescents receiving therapy for depression. This study draws on data from 406 participants of the IMPACT study, a randomized controlled trial, investigating three types of therapy in the treatment of adolescent depression. Logistic regression was used to estimate the effects of predictors on the odds of dropout. Few pre-treatment predictors of dropout were found, with the only significant predictors being older age, antisocial behaviour, and lower scores of verbal intelligence. Missed sessions and poorer therapeutic alliance early in treatment also predicted dropout. Most child and family factors investigated were not significantly associated with dropout. There may be little about depressed adolescents' presentation prior to therapy starting that indicates their risk of dropout. However, within-treatment factors indicated that warning signs of dropout may be identifiable during the initial phase of therapy. Identifying and targeting early treatment indicators of dropout may provide possibilities for improving engagement. Clinical and methodological significance of this article: In the literature, a great deal of attention has been paid to child and family factors that predict therapy dropout, yet in this study, few pre-treatment characteristics were predictive of dropout. However, findings revealed possible warning signs of dropout in the early part of treatment, as poor therapeutic alliance and missed sessions were both found to be predictive of dropout. These findings call for therapists to be aware of such warning signs and clinical guidelines for managing cases at risk of dropout are warranted.

Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.

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Huang, Zhen; Tong, Hongfei; Li, Yuan; Zhou, Haixia; Qian, Jiangchao; Wang, Juxiang; Ruan, Jichen

2017-08-01

The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA. A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy. Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml -1 and 45.3 ± 8.8 pg ml -1 , p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml -1 in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml -1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05). The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.

Merkel Cell Carcinoma in Immunosuppressed Patients

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

2014-06-27

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

Merkel Cell Carcinoma in Immunosuppressed Patients

International Nuclear Information System (INIS)

Ma, Janice E.; Brewer, Jerry D.

2014-01-01

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

Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

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Gorevski, Elizabeth; Succop, Paul; Sachdeva, Jyoti; Cavanaugh, Teresa M; Volek, Paul; Heaton, Pamela; Chisholm-Burns, Marie; Martin-Boone, Jill E

2013-01-01

To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients' adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited "low openness" scores were 91% more likely to be nonadherent. Kidney transplant patients' physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients' adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence.

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

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Raghavan Chinnadurai

2013-01-01

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

Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia.

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Zhang, Xia; Li, Zhangzhi; Geng, Wei; Song, Bin; Wan, Chucheng

2018-07-01

To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients. Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used. After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (paplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment. UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients. © Copyright: Yonsei University College of Medicine 2018.

Two rare cases of Epstein-Barr virus-associated lymphoproliferative disorders in inflammatory bowel disease patients on thiopurines and other immunosuppressive medications.

Science.gov (United States)

Subramaniam, K; Cherian, M; Jain, S; Latimer, M; Corbett, M; D'Rozario, J; Pavli, P

2013-12-01

The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Incidence of herpes zoster amongst adults varies by severity of immunosuppression.

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Schröder, Carsten; Enders, Dirk; Schink, Tania; Riedel, Oliver

2017-09-01

We examined the incidence of herpes zoster in immunocompromised adults (≥18 years) with different severities of immunosuppression and assessed the prevalence of complications and of various kinds of healthcare resource utilisation. German claims data from more than ten million adults were used to calculate annual incidence rates of herpes zoster for the years 2006-2012 and to analyse the prevalence of complications, physician visits, hospitalisations, and antiviral and analgesic treatments using a cohort design. The analyses were stratified by age, sex, and severity of immunosuppression, defined by immunocompromising conditions and drug therapies. The incidence rate per 1000 person-years of herpes zoster was almost twice as high in immunocompromised patients (11.5 (95% confidence interval (CI): 11.4-11.6)) compared to immunocompetent subjects (5.9 (95% CI: 5.8-5.9)). The incidence rate was higher in highly immunocompromised patients (13.4 (95% CI: 13.2-13.6)) than in patients with a low severity of immunosuppression (10.0 (95% CI: 9.8-10.1)). These differences were observed for both sexes and in all age groups. Complications, outpatient physician visits, hospitalisations, and analgesic treatments occurred more frequently in immunocompromised patients as well. Our results show that immunocompromised individuals are affected by the disease in particular and that the burden of herpes zoster is highest in severely immunocompromised patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

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Asami Hanazawa

2018-02-01

Full Text Available The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs, and tumor-associated macrophages (TAMs that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg mouse strain, human interleukin (hIL-6-expressing NOG mice (NOG-hIL-6 transgenic mice. After transplantation of human hematopoietic stem cells (HSCs, the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF, and vascular endothelial growth factor (VEGF, into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1, IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory/immunosuppressive

Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

Czech Academy of Sciences Publication Activity Database

Hájková, Michaela; Heřmánková, Barbora; Javorková, Eliška; Boháčová, Pavla; Zajícová, Alena; Holáň, Vladimír; Krulová, Magdaléna

2017-01-01

Roč. 13, č. 1 (2017), s. 104-115 ISSN 1550-8943 R&D Projects: GA ČR(CZ) GA14-12580S; GA MŠk(CZ) LO1508; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : mesenchymal stem cells * immunosuppressive drugs * stem cell therapy Subject RIV: FF - HEENT, Dentistry OBOR OECD: Immunology Impact factor: 2.967, year: 2016

Nursing care of patients receiving interventional therapy for hepatic artery stenosis after liver transplantation

International Nuclear Information System (INIS)

Wei Lin; Liu Shiguang

2009-01-01

Objective: To discuss the perioperative nursing care of patients who is going to receive interventional therapy for hepatic artery stenosis after liver transplantation and to provide useful reference for reducing surgery-related complication and for improving the prognosis of patients. Methods: Based on the patient's condition and operative requirement,we provided effective nursing care for 20 patients who were admitted to receive the interventional therapy for hepatic artery stenosis after liver transplantation. The nursing care included preoperative preparation,postoperative nursing and medical guidance at the time of discharge. Results: Interventional therapy was successfully performed in all 20 cases, and no hemorrhagic tendency or acute thrombosis occurred. Marked symptomatic improvement was obtained in all patients. Conclusion: The interventional therapy is an effective treatment for hepatic artery stenosis after liver transplantation. Intensive perioperative nursing care can well prevent the occurrence of surgery-related complications and can surely improve the therapeutic results. (authors)

Immunosuppression by non-ionising and ionising radiation - are there similarities?

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Reeves, V.

2003-01-01

Solar UV radiation, the ubiqitous environmental non-ionising radiation, initiates its immunomodulating effects almost entirely in the skin. In direct contrast, ionising radiation penetrates much more efficiently, and has a multitude of internal targets throughout the body. As a consequence, the mechanisms underlying UV-induced immunosuppression have been more readily characterised, whereas surprisingly little is known about immunosuppression resulting from ionising radiation. Photoimmunological studies in mice during the past 20-30 years have established the action spectrum for UV-induced immunosuppression, implicating the UVB waveband, 290-320 nm. Controversy rages over the immunosuppressive potential of the UVA waveband, 320-400 nm, but we demonstrate that environmentally relevant doses of UVA not only are immunologically innocuous, but provide protection against UVB-immunosuppression. Increasingly larger UVA exposures increasingly immunosuppress mice. The UVA immunoprotective effect is strongly dependent on the induction of a cutaneous redox-regulated enzyme, haem oxygenase (heat shock protein 32) that is known to protect cells from oxidative stress, and it is consistent that a number of exogenous antioxidants (vitamin E, vitamin C, green tea polyphenols, isoflavones) can protect effectively from photoimmuno-suppression. Thus the UV-immunosuppressed state is promoted by oxidative damage and depletion of endogenous antioxidant molecules. It is also associated with cutaneous cytokine derangements, such that Th-2 cytokines (IL-4, IL-10) are increased at the expense of Th-1 cytokines (IFN-gamma, IL-12), and with histamine and inflammatory prostaglandin activity. In contrast, immunoprotective UVA irradiation protects the cutaneous cytokine array, inhibits IL-10 upregulation and increases IFN-gamma and IL-12 expression. On the other hand, while ionising radiation is known to cause immunosuppression, large doses target the bone marrow and haemopoiesis lethally and

Characteristics of Hemorrhagic Peptic Ulcers in Patients Receiving Antithrombotic/Nonsteroidal Antiinflammatory Drug Therapy

OpenAIRE

Nakamura, Kazuhiko; Akahoshi, Kazuya; Ochiai, Toshiaki; Komori, Keishi; Haraguchi, Kazuhiro; Tanaka, Munehiro; Nakamura, Norimoto; Tanaka, Yoshimasa; Kakigao, Kana; Ogino, Haruei; Ihara, Eikichi; Akiho, Hirotada; Motomura, Yasuaki; Kabemura, Teppei; Harada, Naohiko

2012-01-01

Background/Aims Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were c...

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

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Viktor Fleming

2018-03-01

Full Text Available The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME, which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.

Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

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Galvão, M M; Peixinho, Z F; Mendes, N F; Sabbaga, E

1997-06-01

Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

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Kurti, Zsuzsanna; Lovasz, Barbara Dorottya; Gecse, Krisztina Barbara; Balint, Anita; Farkas, Klaudia; Morocza-Szabo, Agnes; Gyurcsanyi, Andras; Kristof, Katalin; Vegh, Zsuzsanna; Gonczi, Lorant; Kiss, Lajos Sandor; Golovics, Petra Anna; Lakatos, Laszlo; Molnar, Tamas; Lakatos, Peter Laszlo

2015-12-01

There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Osteoporosis prophylaxis in patients receiving chronic glucocorticoid therapy

International Nuclear Information System (INIS)

Ali, Mir Sadat; AlElq, Abdulmohsen H.; AlShafei, Badar A.; AbuJubarac, Mohammed A.; AlTurki, Haifa A.

2009-01-01

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, yet few patients receive proper measures to prevent its development. We retrospectively searched prescription records to determine if patients receiving oral prednisolone were receiving prophylaxis or treatment for osteopenia and osteoporosis. Patients who were prescribed greater or equal to 7.5 milligrams of prednisolone for 6 months or longer during a 6- month period were identified through the prescription monitoring system. Demographic and clinical data were extracted from the patient records, and dual energy x-ray absorptiometry (DEXA) scans were retrieved, when available. Use of oral calcium, vitamin D and anti-resorptives was recorded. One hundred males and 65 females were receiving oral prednisolone for a mean (SD) duration of 40.4 (29.9) months in males and 41.2 (36.4) months in females. Twenty-one females (12.7%) and 5 (3%) males had bone mineral density measured by DEXA. Of those, 10 (47.6%) females and 3 (50%) males were osteoporotic and 11(52.4%) females and 2 (40%) males were osteopenic. Calcium and vitamin D were prescribed to the majority of patients (60% to 80%), but none were prescribed antiresorptive/anabolic therapy. Patients in this study were neither investigated properly nor treated according to the minimum recommendations for the management of GIOP. Physician awareness about the prevention and treatment of GIOP should be a priority for the local health care system. (author)

Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

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Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

2017-05-01

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

LENUS (Irish Health Repository)

Olaitan, Oyedolamu K

2010-02-01

To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.

Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

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

2014-01-01

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

Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

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Zhao, Li; Zhu, Huanling; Han, Bing; Wang, Lixin; Sun, Yuming; Lu, Xiaojun; Huang, Chunyan; Tan, Bin; Chen, Chunxia; Qin, Li

2018-04-01

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help?

Science.gov (United States)

Nerini, Erika; Bruno, Fulvio; Citterio, Franco; Schena, Francesco P

2016-10-01

End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance.

Modified immunosuppressive therapy with porcine antilymphocyte globulin plus delayed cyclosporine A in children with severe aplastic anemia.

Science.gov (United States)

Cui, Qingya; Sha, Pingping; Chen, Haifei; Shen, Hongshi; Qin, Longmei; Li, Zhengyang; Wu, Tianqin; Wang, Zhaoyue

2018-01-01

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard treatment for children with severe aplastic anemia (SAA) with no human leukocyte antigen-matched siblings. Due to the unavailability of horse ATG in China, porcine antilymphocyte globulin (p-ALG), which is less expensive and more effective than rabbit ATG, is widely used. We sought to evaluate the efficacy and safety profile of modified IST with p-ALG plus delayed CsA at day 21 in 50 SAA children. Eighteen SAA patients who progressed from nonsevere aplastic anemia (NSAA) were classified as SAA-II; the other 32 patients were classified as SAA-I. Overall response (OR) rates at 3, 6 and 12 months were 56, 64 and 62%, respectively. The 10-year overall survival (OS) rate and disease-free survival (DFS) rate were 80 and 56%. The OR, OS and DFS rates in the SAA-I group were clearly better than those in the SAA-II group. Death rate from infection within 30 days was 4%. Modified IST with p-ALG plus delayed CsA is a reliable and well-tolerated treatment for children with SAA, and reduces early death due to infection. Modified IST is more suitable for children with SAA-I.

Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

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Helmschrott M

2017-06-01

Full Text Available Matthias Helmschrott,1 Rasmus Rivinius,1 Thomas Bruckner,2 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, 2Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: A calcineurin inhibitor (CNI-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs seems to be attractive in patients after heart transplantation (HTX in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC-based vs cyclosporine-A (CSA-based immunosuppression (in combination with mycophenolate mofetil. However, data regarding renal function after HTX in mTOR/CNI patients remain limited. Aim: Primary end point of the present study was to analyze renal function in HTX patients 1 year after switch to an mTOR/CNI-based immunosuppression. Methods: Data of 80 HTX patients after change to mTOR/CNI-based immunosuppression were retrospectively analyzed. Renal function was assessed by measured serum creatinine and by estimated glomerular filtration rate (eGFR calculated from Modification of Diet in Renal Disease equation. Results: Twenty-nine patients received mTOR/CSA-based treatment and 51 patients received mTOR/TAC-based therapy. At time of switch and at 1-year follow-up, serum creatinine and eGFR did not differ significantly between both study groups (all P=not statistically significant. Analysis of variances with repeated measurements detected a similar change of renal function in both study groups. Conclusion: The present study detected no significant differences between both mTOR/CNI study groups, indicating a steady state of renal function in HTX patients after switch of immunosuppressive regimen. Keywords: heart transplantation, cyclosporine A, tacrolimus, risk factors

Skeletal mass in patients receiving chronic anticonvulsant therapy

Energy Technology Data Exchange (ETDEWEB)

Zanzi, I.; Roginsky, M.S.; Rosen, A.; Cohn, S.H.

1981-01-01

The technique of in vivo total body neutron activation analysis was used to measure total body calcium (TBCa), a sensitive and precise index of skeletal mass, expressed as the Ca ratio (TBCa observed/TBCa predicted). 23 unselected, ambulatory, noninstitutionalized, adult epileptic patients under long-term anticonvulsant therapy were studied. Ca ratio was normal in 20 of the patients, low in only 2 and borderline in 1 patient. Plasma alkaline phosphatase values were elevated in half the subjects. Plasma Ca (uncorrected) was in the normal range in all. Serum 25-hydroxvitamin D (25-OHD) was low in 67% of the subjects, but only 1 patient had a value below 5 ng/ml. There was no correlation between the Ca ratio and the alkaline phosphatase or 25-OHD values. No radiographic or other evidences of osteomalacia were observed. This study does not support the notion of a prevalence of osteopenia in ambulatory, noninstitutionalized, adult epileptic patients receiving chronic anticonvulsant therapy in this geographical area despite the frequent findings of biochemical abnormalities.

Stent patency in patients with distal malignant biliary obstruction receiving chemo(radio)therapy

Science.gov (United States)

Haal, Sylke; van Hooft, Jeanin E.; Rauws, Erik A. J.; Fockens, Paul; Voermans, Rogier P.

2017-01-01

Background and study aims  Recent literature suggests that chemo(radio)therapy might reduce the patency of plastic stents in patients with malignant biliary obstruction. Whether this might also be valid for other types of stents is unknown. The aim of this study was to determine the influence of chemo(radio)therapy on the patency of fully-covered self-expandable metal stents (FCSEMSs) and plastic stents. Patients and methods  We retrospectively reviewed the electronic medical records of patients with distal malignant biliary obstruction who underwent biliary stent placement between April 2001 and July 2015. Primary outcome was duration of stent patency. Secondary outcome was stent patency at 3 and 6 months. We used Kaplan–Meier survival analyses to compare stent patency rates between patients who received chemo(radio)therapy and patients who did not. Results  A total of 291 biliary stents (151 metal and 140 plastic) were identified. The median cumulative stent patency of FCSEMSs did not differ between patients receiving chemo(radio)therapy (n = 51) and those (n = 100) who did not ( P  = 0.70, log-rank test). The estimated cumulative stent patency of plastic stents was also comparable in 99 patients without and 41 patients with chemo(radio)therapy ( P  = 0.73, log-rank test). At 3 and 6 months, FCSEMS patency rates were 87 % and 83 % in patients without chemo(radio)therapy and 96 % and 83 % in patients with therapy, respectively. Plastic patency rates were 69 % and 55 % in patients without and 85 % and 39 % in patients with therapy, respectively. After 1 year, 78 % of the FCSEMSs were still patent in patients without chemo(radio)therapy and 69 % of the FCSEMSs were still patent in patients with therapy. Conclusion  Our data indicate that chemo(radio)therapy does not reduce the patency of biliary fully-covered metal and plastic stents. PMID:29090242

Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy

International Nuclear Information System (INIS)

Martins, Flavia Paiva Proenca; Gutfilen, Bianca

2001-01-01

Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed 99m Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

Directory of Open Access Journals (Sweden)

Welling JD

2012-04-01

Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

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Michaud L

2016-12-01

Full Text Available Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20 might have lower medication adherence than noncomplex patients (INTERMED≤20. Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20. Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11 and noncomplex patients (N=21 were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value. Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly

Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

Science.gov (United States)

Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

2010-05-01

No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

A tacrolimus-related immunosuppressant with reduced toxicity.

Science.gov (United States)

Dumont, F J; Koprak, S; Staruch, M J; Talento, A; Koo, G; DaSilva, C; Sinclair, P J; Wong, F; Woods, J; Barker, J; Pivnichny, J; Singer, I; Sigal, N H; Williamson, A R; Parsons, W H; Wyvratt, M

1998-01-15

Tacrolimus (FK506) has potent immunosuppressive properties reflecting its ability to block the transcription of lymphokine genes in activated T cells through formation of a complex with FK506 binding protein-12, which inhibits the phosphatase activity of calcineurin. The clinical usefulness of tacrolimus is limited, however, by severe adverse effects, including neurotoxicity and nephrotoxicity. Although this toxicity, like immunosuppression, appears mechanistically related to the calcineurin inhibitory action of the drug, a large chemistry effort has been devoted to search for tacrolimus analogs with reduced toxicity but preserved immunosuppressive activity that might have enhanced therapeutic utility. Here, we report on the identification of such an analog, which was synthetically derived from ascomycin (ASC), the C21 ethyl analog of tacrolimus, by introducing an indole group at the C32 position. The profile of biological activity of indolyl-ASC was characterized in rodent models of immunosuppression and toxicity. Indolyl-ASC was found to exhibit an immunosuppressive potency equivalent to that of tacrolimus in T-cell activation in vitro and in murine transplant models, even though indolyl-ASC bound about 10 times less to intracellular FK506 binding protein-12 than tacrolimus or ASC. Further evaluation of indolyl-ASC revealed that it is threefold less potent than tacrolimus in inducing hypothermia, a response that may reflect neurotoxicity, and in causing gastrointestinal transit alterations in mice. Moreover, indolyl-ASC was at least twofold less nephrotoxic than tacrolimus upon 3-week oral treatment in rats. Altogether, these data indicate a modest but definite improvement in the therapeutic index for indolyl-ASC compared with tacrolimus in rodent models.

[Clinical views from the forefront of immunosuppressive drugs].

Science.gov (United States)

Kobayashi, Eiji

2005-11-01

Recently, many immunosuppressants have been developed and some of them have already been introduced in clinical organ transplantation. With a new concept of immunoregulation, which focuses on prevention of rejection and over-immunosuppression, the latest protocol has been conducted. Chimeric or humanized antibodies targeting the lymphocyte surface molecule such as CD19, 20, 25, 40, and 52 are administrated in the induction phase, and calcineurin inhibitors (cyclosporin and tacrolimus) are used as key drugs. For tapering the doses of them, the combined application of anti-metabolic agents of azathioprine, mizoribine, or mycophenolate mofetil (MMF) has been proved effective. Lymphocyte forming drugs induce unique immunoregulation, targeting at sphingosine 1-phosphate (SlP) receptors. FTY720 is now in the procedure of clinical trial to compare with MMF. KRP203 is also a candidate for more specific SIP receptor agonist. In this issue, I reviewed the recent immunosuppressive strategy and focused on the advance of novel immunosuppressive drugs.

Immunosuppressive agents are associated with peptic ulcer bleeding.

Science.gov (United States)

Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2017-05-01

Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ 2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ 2 , and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at

Unusual Case Report of Thrombotic Microangiopathy of the Small Bowel Following Liver Transplantation, a Possible Immunosuppressant-Induced Disease with Histological and Ultrastructural Findings

Directory of Open Access Journals (Sweden)

Domenico Piscitelli

2009-01-01

Full Text Available Cyclosporin-A (CsA and tacrolimus (FK-506 are immunomodulating agents used to prevent rejection in organ transplantation. They are both associated with several side effects, including nephrotoxicity and severe hypertension due to vascular injury, which often appears as a microvascular occlusive disorder (thrombotic microangiopathy, TMA. We report the first case of a microvascular occlusive disorder with the features of TMA in the small bowel of an orthotopic liver transplant (OLT patient after immunosuppressive therapy with CsA and FK506. The patient presented with severe recurrent abdominal colics and distal subocclusion, requiring aggressive surgical treatment. Histological and ultrastructural analysis of the resected specimen disclosed intestinal TMA. Although rare, such a complication should be considered in the differential diagnosis of abdominal colics in patients undergoing immunosuppressant therapy after OLT.

Reiki Therapy for Symptom Management in Children Receiving Palliative Care: A Pilot Study.

Science.gov (United States)

Thrane, Susan E; Maurer, Scott H; Ren, Dianxu; Danford, Cynthia A; Cohen, Susan M

2017-05-01

Pain may be reported in one-half to three-fourths of children with cancer and other terminal conditions and anxiety in about one-third of them. Pharmacologic methods do not always give satisfactory symptom relief. Complementary therapies such as Reiki may help children manage symptoms. This pre-post mixed-methods single group pilot study examined feasibility, acceptability, and the outcomes of pain, anxiety, and relaxation using Reiki therapy with children receiving palliative care. A convenience sample of children ages 7 to 16 and their parents were recruited from a palliative care service. Two 24-minute Reiki sessions were completed at the children's home. Paired t tests or Wilcoxon signed-rank tests were calculated to compare change from pre to post for outcome variables. Significance was set at P Reiki therapy did decrease pain, anxiety, heart, and respiratory rates, but small sample size deterred statistical significance. This preliminary work suggests that complementary methods of treatment such as Reiki may be beneficial to support traditional methods to manage pain and anxiety in children receiving palliative care.

Immunosuppressive T-cell antibody induction for heart transplant recipients

DEFF Research Database (Denmark)

Penninga, Luit; Møller, Christian H; Gustafsson, Finn

2013-01-01

Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

Cutaneous toxoplasmosis in an immunosuppressed dog

Directory of Open Access Journals (Sweden)

T.S. Oliveira

2014-06-01

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

A pilot study of exercise in men with prostate cancer receiving androgen deprivation therapy

International Nuclear Information System (INIS)

Lee, C Ellen; Leslie, William D; Lau, YK James

2012-01-01

Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT. A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data. Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical

Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-12-28

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.

Music Therapy is Associated With Family Perception of More Spiritual Support and Decreased Breathing Problems in Cancer Patients Receiving Hospice Care.

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Burns, Debra S; Perkins, Susan M; Tong, Yan; Hilliard, Russell E; Cripe, Larry D

2015-08-01

Music therapy is a common discretionary service offered within hospice; however, there are critical gaps in understanding the effects of music therapy on hospice quality indicators, such as family satisfaction with care. The purpose of this study was to examine whether music therapy affected family perception of patients' symptoms and family satisfaction with hospice care. This was a retrospective, cross-sectional analysis of electronic medical records from 10,534 cancer patients cared for between 2006 and 2010 by a large national hospice. Logistic regression was used to estimate the effect of music therapy using propensity scores to adjust for non-random assignment. Overall, those receiving music therapy had higher odds of being female, having longer lengths of stay, and receiving more services other than music therapy, and lower odds of being married/partnered or receiving home care. Family satisfaction data were available for 1495 (14%) and were more likely available if the patient received music therapy (16% vs. 12%, P music therapy vs. those not. Patients who received music therapy were more likely to report discussions about spirituality (odds ratio [OR] = 1.59, P = 0.01), had marginally less trouble breathing (OR = 0.77, P = 0.06), and were marginally more likely to receive the right amount of spiritual support (OR = 1.59, P = 0.06). Music therapy was associated with perceptions of meaningful spiritual support and less trouble breathing. The results provide preliminary data for a prospective trial to optimize music therapy interventions for integration into clinical practice. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A systematic review of oral fungal infections in patients receiving cancer therapy

NARCIS (Netherlands)

Lalla, Rajesh V.; Latortue, Marie C.; Hong, Catherine H.; Ariyawardana, Anura; D'Amato-Palumbo, Sandra; Fischer, Dena J.; Martof, Andrew; Nicolatou-Galitis, Ourania; Patton, Lauren L.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.

Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications

OpenAIRE

Pourmand, G. R.; Dehghani, S.; Saraji, A.; Khaki, S.; Mortazavi, S. H.; Mehrsai, A.; Sajadi, H.

2012-01-01

Background: Wound healing disorders are probably the most common post-transplantation surgical complications. It is thought that wound healing disturbance occurs due to antiproliferative effects of immunosuppressive drugs. On the other hand, success of transplantation is dependent on immunosuppressive therapies. Antihuman thymocyte globulin (ATG) has been widely used as induction therapy but the impact of this treatment on wound healing is not fully understood. Objective: To investigate wound...

Immunosuppressive effect of total lymphoid irradiation

International Nuclear Information System (INIS)

Bendel, V.; Medizinische Hochschule Hannover

1981-01-01

Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

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

Science.gov (United States)

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

2014-12-01

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

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

Science.gov (United States)

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.

Influence Of Ginger (Zingiber Officinale) Supplementation Against GAMMA Rays Induced Immunosuppression In Male Rats

International Nuclear Information System (INIS)

Mangood, S.A.; Kassab, F.M.A.

2013-01-01

The influence of ginger (Zingiber officinale) supplementation against gamma rays-induced immunosuppression in male albino rats was investigated in the present study. Twenty four male albino rats were divided into four equal groups; control group (receiving no treatment), ginger group where the rats received ginger orally at a dose of 15 g/rat/day for 120 consecutive days, gamma radiation group which subjected to a single 6 Gy whole body gamma radiation and gamma radiation plus ginger group where each rat after taking daily 15 g of ginger for 120 consecutive days was subjected to 6 Gy whole body irradiation. Complete blood pictures and immunoglobulin G (IgG) and M (IgM) were estimated and spleen tissue was also examined histologically. The data obtained revealed that exposure to 6 Gy of gamma radiation caused significant decrease in the body weight, spleen weight, IgG, IgM, erythroide and leucoid elements and produced histological damage in spleen tissue. On the other hand, ginger as a protective agent, caused significant amelioration in the changes produced by irradiation especially immunoglobulins leading to the conclusion that ginger supplementation for 120 days caused modulation of the humoral immune response in irradiated rats. In conclusion, these findings indicated that ginger has the regulatory effect against gamma rays-induced immunosuppression.

Listeria monocytogenes meningitis in an atomic bomb survivor receiving corticosteroid therapy for aplastic anemia

Energy Technology Data Exchange (ETDEWEB)

Fujihara, Kazuo; Shida, Norihiko; Ohta, Michiya [Hiroshima Atomic Bomb Hospital (Japan)

1995-12-01

We report a case of successfully treated Listeria monocytogenes (Lm) meningitis in a atomic bomb survivor receiving steroid therapy for aplastic anemia. The patient was a 62-year-old woman and the past medical history included hypothyroidism due to radioiodide therapy for Basedow disease, breast cancer, aplastic anemia, steroid-induced diabetes mellitus, and pulmonary tuberculosis. At the time of onset, she was receiving corticosteroid, anabolic steroid, an H{sub 2}-blocker (famotidine), and other medication. Since she developed symptoms of meningitis when she visited our hospital for regular medical check-up for aplastic anemia, she was hospitalized and given antibiotic therapy, including ABPC, without delay. With this effective antibiotic therapy and successful management of the co-existing medical conditions, she was cured except for being a little euphoric. Lm meningitis is known to occur in aged and immunocompromised patients. Since most of the atomic bomb survivors are now aged and the prevalence of malignancy, diabetes mellitus, and other diseases which cause immunodeficiency have been rising year by year, Lm meningitis is one of the emergency neurologic conditions whose diagnosis should not be delayed in this population. (author).

Listeria monocytogenes meningitis in an atomic bomb survivor receiving corticosteroid therapy for aplastic anemia

International Nuclear Information System (INIS)

Fujihara, Kazuo; Shida, Norihiko; Ohta, Michiya

1995-01-01

We report a case of successfully treated Listeria monocytogenes (Lm) meningitis in a atomic bomb survivor receiving steroid therapy for aplastic anemia. The patient was a 62-year-old woman and the past medical history included hypothyroidism due to radioiodide therapy for Basedow disease, breast cancer, aplastic anemia, steroid-induced diabetes mellitus, and pulmonary tuberculosis. At the time of onset, she was receiving corticosteroid, anabolic steroid, an H 2 -blocker (famotidine), and other medication. Since she developed symptoms of meningitis when she visited our hospital for regular medical check-up for aplastic anemia, she was hospitalized and given antibiotic therapy, including ABPC, without delay. With this effective antibiotic therapy and successful management of the co-existing medical conditions, she was cured except for being a little euphoric. Lm meningitis is known to occur in aged and immunocompromised patients. Since most of the atomic bomb survivors are now aged and the prevalence of malignancy, diabetes mellitus, and other diseases which cause immunodeficiency have been rising year by year, Lm meningitis is one of the emergency neurologic conditions whose diagnosis should not be delayed in this population. (author)

Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy.

Science.gov (United States)

Soliman, Hend; Abdel Hady, Aisha Fawzy; Abdel Hamid, Asmaa; Mahmoud, Heba

2016-01-01

The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. The younger group reached average Arabic language scores, while the older group showed moderate language delay. Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings. © 2016 S. Karger AG, Basel.

Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: clues for possible immunosuppression-related or infectious etiology.

Science.gov (United States)

Shiels, Meredith S; Engels, Eric A

2012-10-01

Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS). Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression). Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression). The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Copyright © 2012 American Cancer Society.

Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2014-01-01

Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

Cost-effectiveness of abiraterone treatment in patients with castration-resistant prostate cancer who previously received docetaxel therapy

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2014-11-01

Full Text Available Background. Therapy for metastatic castration-resistant prostate cancer (CRPC is a serious problem that requires significant public health care expenditures.Objective: to evaluate the cost-effectiveness of abiraterone treatment in patients with metastatic CRPC who previously received docetaxel under the conditions of the budgetary public health system of the Russian Federation.Material and methods. Markovian simulation based on the COU-AA-301 randomized placebo-controlled Phase III study was used. Survival analysis was made in 70-year-old patients. The cost of abiraterone therapy corresponded to that of the 2013 auctions.Results. Abiraterone therapy in patients who have previously received docetaxel therapy causes an increase in average life expectancy by an average of 4.6 months and progression-free survival by 2.0 months. Moreover, the cost calculated with reference to one year of additional life will account for about 3.6 million rubles and that to one additional quality-adjusted life year will be about 5.45 million rubles.Conclusion. The cost-effectiveness of abiraterone therapy for metastatic CRPC in patients who have previously received docetaxel therapy is similar to that of other medicaments used in oncological practice under the conditions of the budgetary public health system of the Russian Federation. In this connection, abiraterone may be considered as an economically acceptable medical intervention in this clinical situation.

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

Directory of Open Access Journals (Sweden)

Helio Tedesco-Silva Jr

2011-01-01

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

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

Science.gov (United States)

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

2006-03-15

Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

Personalization of the Immunosuppressive Treatment in Renal Transplant Recipients: The Great Challenge in “Omics” Medicine

Directory of Open Access Journals (Sweden)

Gianluigi Zaza

2015-02-01

Full Text Available Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%–5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, “omics” techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient’s genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies.

Selective immunosuppression by radiation

International Nuclear Information System (INIS)

Chanana, A.D.; Cronkite, E.P.; Joel, D.D.

1976-01-01

The historical aspects of selective irradiation of lymphocytes are reviewed as well as the problems concerned with dosimetry and the radiosensitivity of circulating blood elements other than lymphocytes. The possibilities of perturbations in steady-state lymphocytopoiesis which might be triggered by products of radiation-induced cell death are presented; however, the parameters investigated thus far, such as the degree of lymphocytopenia, thoracic duct lymphocyte output, and cell-cycle times of thoracic duct lymphocytes, have failed to reveal any such perturbations. Studies in adrenalectomized calves have failed to confirm the notion that lymphocytopenia after extracorporeal irradiation of blood and lymph might primarily be accounted for by stress-induced corticosteroid hormonal activity. Of the various techniques, only local-graft irradiation and extracorporeal irradiation of blood (ECIB) have found clinical application. The results obtained are encouraging and indicate a need for additional, well-controlled clinical trials, especially concerning the role of ECIB as an adjunct to standard immunosuppressive therapy. The experimental results with extracorporeal irradiation of lymph have also established the potential of this technique for clinical application. There is an urgent need for studying the influence of irradiation on various subpopulations of lymphocytes with regard to their functional capabilities and in particular with regard to their reproductive potential. Possible influence of selective blood irradiation on circulating stem cells in blood needs to be evaluated

Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

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Hisanao Akiyama

Full Text Available The first non-vitamin K antagonist oral anticoagulant (NOAC introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH.We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014.ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years. Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy.

Sequential kidney/islet transplantation using prednisone-free immunosuppression.

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Kaufman, Dixon B; Baker, Marshall S; Chen, Xiaojuan; Leventhal, Joseph R; Stuart, Frank P

2002-08-01

Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet-after-kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8-10,000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet-after-kidney transplantation is described using the steroid-free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265,888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95% (trypan blue exclusion); and d) mean islet potency (static low-high glucose challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty-four-hour continuous glucose monitoring confirmed moment-to-moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study.

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Brito, Daniela Cristina Sampaio de; Marsicano, Elisa Oliveira; Grincenkov, Fabiane Rossi Dos Santos; Colugnati, Fernando Antônio Basile; Lucchetti, Giancarlo; Sanders-Pinheiro, Helady

2016-01-01

: Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P transplantation patients and should be considered among the strategies for reducing nonadherence.

Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent  Clostridium difficile Infection

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Hadeel Zainah

2012-01-01

Full Text Available We report a case of ulcerative colitis (UC and recurrent Clostridium difficile infection (CDI where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.

Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

International Nuclear Information System (INIS)

Waer, M.; Ang, K.K.; Vandeputte, M.; Van der Schueren, E.

1982-01-01

Three groups of C 57 /BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different perameters involved in the transplantation

Amniotic membrane transplantation ineffective as additional therapy in patients with aggressive Mooren's ulcer.

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Schallenberg, Maurice; Westekemper, Henrike; Steuhl, Klaus-Peter; Meller, Daniel

2013-12-17

Mooren's ulcer is a severe ulcerative inflammation of the cornea. The exact pathogenesis remains unclear. Therefore many therapies of Mooren's ulcer are recommended in literature. To shed more light on the ongoing question of optimal treatment of severe progressive Mooren's ulcer, we here report on a retrospective case series of patients treated with systemic immunosuppressive therapy and additional amniotic membrane transplantation. Medical records from seven patients (eleven eyes), 4 male and 3 female, with severe progressive Mooren's ulcer were analysed retrospectively. The mean follow up was 88.4 ± 80.8 months (range 12-232 month). A HLA-typing was performed in all patients. A systemic immunosuppressive therapy was administered in all patients. The amniotic membrane was transplanted after the base of the ulcer was resected. Multiple amniotic membrane transplantations were necessary in six patients. The visual outcome of all patients was poor. No patient achieved a visual acuity better than 20/630 Snellen chart. Five patients were positive for HLA-DQ2 and four patients were positive for HLA-DR17(3). The aggressive and highly inflammatory form of Mooren's ulcer is difficult to treat and the progression of the disease is hard to influence positively even under systemic immunosuppressive therapy. Therefore, the main intention of therapy is to achieve a stable epithelialized corneal surface without the risk of perforation. Amniotic membrane transplantation is not able to cure severe forms of Mooren's ulcer. However it supports the immunosuppressive therapy in acute situations as in critical corneal thinning.

The effect of music therapy on physiological signs of anxiety in patients receiving mechanical ventilatory support.

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Korhan, Esra Akin; Khorshid, Leyla; Uyar, Mehmet

2011-04-01

The aim of this study was to investigate if relaxing music is an effective method of reducing the physiological signs of anxiety in patients receiving mechanical ventilatory support. Few studies have focused on the effect of music on physiological signs of anxiety in patients receiving mechanical ventilatory support. A study-case-control, experimental repeated measures design was used. Sixty patients aged 18-70 years, receiving mechanical ventilatory support and hospitalised in the intensive care unit, were taken as a convenience sample. Participants were randomised to a control group or intervention group, who received 60 minutes of music therapy. Classical music was played to patients using media player (MP3) and headphones. Subjects had physiological signs taken immediately before the intervention and at the 30th, 60th and 90th minutes of the intervention. Physiological signs of anxiety assessed in this study were mean systolic and diastolic blood pressure, pulse rate, respiratory rate and oxygen saturation in blood measured by pulse oxymetry. Data were collected over eight months in 2006-2007. The music group had significantly lower respiratory rates, and systolic and diastolic blood pressure, than the control group. This decrease improved progressively in the 30th, 60th and 90th minutes of the intervention, indicating a cumulative dose effect. Music can provide an effective method of reducing potentially harmful physiological responses arising from anxiety. As indicated by the results of this study, music therapy can be supplied to allay anxiety in patients receiving mechanical ventilation. Nurses may include music therapy in the routine care of patients receiving mechanical ventilation. © 2011 Blackwell Publishing Ltd.

Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study.

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Kernéis, Solen; Launay, Odile; Ancelle, Thierry; Iordache, Laura; Naneix-Laroche, Véronique; Méchaï, Frédéric; Fehr, Thierry; Leroy, Jean-Philippe; Issartel, Bertrand; Dunand, Jean; van der Vliet, Diane; Wyplosz, Benjamin; Consigny, Paul-Henri; Hanslik, Thomas

2013-09-01

To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy. All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids. Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination. After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results. Copyright © 2013 by the American College of Rheumatology.

The prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy.

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Savage, Nathan J; Fritz, Julie M; Kircher, John C; Thackeray, Anne

2015-03-01

To investigate the prognostic value of electrodiagnostic testing in patients with sciatica receiving physical therapy. Electrodiagnostic testing was performed on 38 patients with sciatica participating in a randomized trial comparing different physical therapy interventions. Patients were grouped and analyzed according to the presence or absence of radiculopathy based on electrodiagnostic testing. Longitudinal data analysis was conducted using multilevel growth modeling with ten waves of data collected from baseline through the treatment and post-treatment periods up to 6 months. The primary outcome measure was changes in low back pain-related disability assessed using the Roland and Morris disability questionnaire (RMDQ). Patients with radiculopathy (n = 19) had statistically significant and clinically meaningful improvements in RMDQ scores at every post-treatment follow-up occasion regardless of treatment received. The final multilevel growth model revealed improvements in RMDQ scores in patients with radiculopathy at the 6-week (-8.1, 95 % CI -12.6 to -2.6; P = 0.006) and 6-month (-4.1, 95 % CI -7.4 to -0.7; P = 0.020) follow-up occasions compared to patients without radiculopathy. Treatment group was not a significant predictive factor at any follow-up occasion. An interaction between electrodiagnostic status and time revealed faster weekly improvements in RMDQ scores in patients with radiculopathy at the 6-week (-0.72, 95 % CI -1.4 to -0.04; P = 0.040) through the 16-week (-0.30, 95 % CI, -0.57 to -0.04; P = 0.028) follow-up occasions compared to patients without radiculopathy. The presence of lumbosacral radiculopathy identified with electrodiagnostic testing is a favorable prognostic factor for recovery in low back pain-related disability regardless of physical therapy treatment received.

Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

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Gorevski E

2013-04-01

Full Text Available Elizabeth Gorevski,1 Paul Succop,1 Jyoti Sachdeva,1 Teresa M Cavanaugh,1 Paul Volek,1 Pamela Heaton,1 Marie Chisholm-Burns,2 Jill E Martin-Boone1 1University of Cincinnati, Cincinnati, OH, USA, 2University of Tennessee College of Pharmacy, Memphis, TN, USA Objectives: To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. Methods: A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients’ adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. Results: A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited “low openness” scores were 91% more likely to be nonadherent. Kidney transplant patients’ physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. Conclusion: The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence. Keywords: adherence, transplant, liver, kidney

Low Adherence to Immunosuppressants Is Associated With Symptom Experience Among Kidney Transplant Recipients.

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Lee, S Y; Chu, S H; Oh, E G; Huh, K H

2015-11-01

The purpose of this study was to investigate the relationship between immunosuppressant-related symptom experience (SE) and adherence to immunosuppressant regimens among kidney transplant (KT) recipients. A total of 239 KT recipients on an immunosuppressant regimen who were followed up after transplantation participated in this study. Data was collected through a self-reported questionnaire survey (medication adherence, SE, and quality of life) and medical record review. Low adherence in the immunosuppressant group was associated with longer time since KT, less comorbidity (adherence among KT recipients showed significantly greater overall symptom occurrence (P = .001) and symptom distress (P = .002) levels than patients with high or medium adherence after adjusting for a number of covariates. The most common symptom both in terms of occurrence (96.4%) and distress (91.1%) among poorly adherent KT recipients was tiredness. Low adherence to an immunosuppressant regimen was significantly associated with high SE among KT recipients. Strategies to decrease immunosuppressant-related SE are needed to improve adherence to immunosuppressants. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

Science.gov (United States)

Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

DEFF Research Database (Denmark)

Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

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Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

2017-01-01

Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction.

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Gharagozloo, Marjan; Majewski, Slawomir; Foldvari, Marianna

2015-05-01

Autoimmune diseases are chronic, destructive diseases that can cause functional disability and multiple organ failure. Despite significant advances in the range of therapeutic agents, especially biologicals, limitations of the routes of administration, requirement for frequent long-term dosing and inadequate targeting options often lead to suboptimal effects, systemic adverse reactions and patient non-compliance. Nanotechnology offers promising strategies to improve and optimize autoimmune disease treatment with the ability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we focus on nanomedicine-based delivery strategies of biological immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis and type 1 diabetes. This comprehensive review details the concepts and clinical potential of novel nanomedicine approaches for inducing immunosuppression and immunological tolerance in autoimmune diseases in order to modulate aberrant and pathologic immune responses. The treatment of autoimmune diseases remains a significant challenge. The authors here provided a comprehensive review, focusing on the current status and potential of nanomedicine-based delivery strategies of immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type 1 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Low-Level Laser therapy on the fungal proliferation of Candida albicans

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Carneiro, Vanda S. M.; Araújo, Natália C.; Menezes, Rebeca F. d.; Moreno, Lara M.; Santos-Neto, Alexandrino d. P.; Gerbi, Marleny Elizabeth M.

2016-03-01

Candida albicans plays an important role in triggering infections in HIV+ patients. The indiscriminate use of antifungals has led to resistance to Candida albicans, which requires new treatment alternatives for oral candidiasis. Low-level laser therapy promotes a considerable improvement in the healing of wounds and in curing illnesses caused by microorganisms. The aim of the present study was to assess the effect of laser radiation on the cell proliferation of Candida albicans in immunosuppressed patients. Six Candida albicans strains that had been isolated from immunosuppressed patients were divided into a control group and experimental groups, which received eight sessions of laser therapy (InGaAlP, λ685nm, P = 30mW, CW, Φ~6 mm and GaAlAs, λ830nm, P = 40mW, CW, Φ~6 mm) using dosimetries of 6J/cm2, 8J/cm2, 10J/cm2 and 12J/cm2 for each wavelength and power. The results were not statistically significant (Kruskal Wallis, p > 0.05), although the proliferation of Candida albicans was lower in some of the experimental groups. The dosimetry of 6J/cm2 (GaAlAs, λ830nm, P = 40mW) provided lower mean scores than the other groups for the growth of Candida. Further studies are required to confirm whetehr laser therapy is a viable option in the treatment of fungal infections.

Cyclosporine A-loaded and stem cell-seeded electrospun nanofibers for cell-based therapy and local immunosuppression

Czech Academy of Sciences Publication Activity Database

Holáň, Vladimír; Chudíčková, Milada; Trošan, Peter; Svobodová, Eliška; Krulová, Magdalena; Kubinová, Šárka; Syková, Eva; Širc, Jakub; Michálek, Jiří; Juklíčková, M.; Munzarová, M.; Zajícová, Alena

2011-01-01

Roč. 156, č. 3 (2011), s. 406-412 ISSN 0168-3659 R&D Projects: GA AV ČR KAN200520804; GA ČR GAP304/11/0653; GA ČR(CZ) GAP301/11/1568; GA ČR GD310/08/H077; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40500505; CEZ:AV0Z50520514 Keywords : nanofibers * immunosuppression * cell transfer Subject RIV: EC - Immunology Impact factor: 5.732, year: 2011

Dendritic Cells Primed with Paracoccidioides brasiliensis Peptide P10 Are Therapeutic in Immunosuppressed Mice with Paracoccidioidomycosis

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Leandro B. R. Silva

2017-06-01

Full Text Available Paracoccidioidomycosis (PCM is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P. brasiliensis Pb18 to establish the therapeutic efficacy of P10-pulsed DCs. Immunosuppressed and infected animals that received DCs had a reduction in their fungal burden, and this result was most pronounced in mice receiving DCs primed with P10. The efficacy of therapeutic DCs was significantly augmented by concomitant treatment with trimethoprim-sulfamethoxazole. Additionally, primed-DCs with or without the antifungal drug induced a beneficial Th1-biased immune response and significantly reduced tissue damage. In conclusion, these studies with immunocompromised mice demonstrate that P10-pulsed DCs with or without concomitant antifungal drugs are potently effective in combating invasive PCM. These findings support further translational studies to validate the use of P10-primed DCs for PCM in immunocompetent and immunosuppressed hosts.

Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.

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Kadis, Darren S; Goshulak, Debra; Namasivayam, Aravind; Pukonen, Margit; Kroll, Robert; De Nil, Luc F; Pang, Elizabeth W; Lerch, Jason P

2014-03-01

Children with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p ≤ 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p ≤ 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.

Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications.

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Carney, R M; Rich, M W; teVelde, A; Saini, J; Clark, K; Freedland, K E

1987-08-01

Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.

Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study.

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Elisa Oliveira Marsicano

Full Text Available Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system.Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods (self-report [i.e., The Basel Adherence Scale for Assessment of Immunossupressives-BAASIS], collateral report, and immunosuppressive blood levels. Multilevel correlations of non-adherence were assessed (macro, meso, micro and patient level. Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence.Our sample consisted primarily of male (65%, Caucasians (72% with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%, with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages (21.6 vs. 4%; OR 6.46 [1.35-30.89], p = 0.009; patient level, and having access to private health insurance (35.3% vs. 18.4%; OR 2.42 [0.96-6.10], p = 0.04; meso level were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model (OR 5.0; IC: 1.01-25.14; p = 0.04.Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously.

Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study.

Science.gov (United States)

Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Antônio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

2015-01-01

Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods (self-report [i.e., The Basel Adherence Scale for Assessment of Immunossupressives-BAASIS], collateral report, and immunosuppressive blood levels). Multilevel correlations of non-adherence were assessed (macro, meso, micro and patient level). Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence. Our sample consisted primarily of male (65%), Caucasians (72%) with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%), with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages (21.6 vs. 4%; OR 6.46 [1.35-30.89], p = 0.009; patient level), and having access to private health insurance (35.3% vs. 18.4%; OR 2.42 [0.96-6.10], p = 0.04; meso level) were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model (OR 5.0; IC: 1.01-25.14; p = 0.04). Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously.

Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia

Energy Technology Data Exchange (ETDEWEB)

Schuster, F R; Hubner, B [Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany); Führer, M [Department of Pediatric Oncology and Hematology, Dr von Haunersches Children' s Hospital, University of Munich, Munich (Germany); Eckermann, O; Gombert, M [Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany); Dornmair, K [Department for Clinical Neuroimmunology, University of Munich, Munich (Germany); Binder, V; Reuther, S; Krell, P [Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany); Keller, T [Acomed, statistical analysis GmbH, Leipzig (Germany); Borkhardt, A [Clinic of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf (Germany)

2011-03-01

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation.

Highly skewed T-cell receptor V-beta chain repertoire in the bone marrow is associated with response to immunosuppressive drug therapy in children with very severe aplastic anemia

International Nuclear Information System (INIS)

Schuster, F R; Hubner, B; Führer, M; Eckermann, O; Gombert, M; Dornmair, K; Binder, V; Reuther, S; Krell, P; Keller, T; Borkhardt, A

2011-01-01

One of the major obstacles of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) comes from the often months-long unpredictability of bone-marrow (BM) recovery. In this prospective study in children with newly diagnosed very severe AA (n=10), who were enrolled in the therapy study SAA-BFM 94, we found a dramatically reduced diversity of both CD4+ and CD8+ BM cells, as scored by comprehensive V-beta chain T-cell receptor (TCR) analysis. Strongly skewed TCR V-beta pattern was highly predictive for good or at least partial treatment response (n=6, CD8+ complexity scoring median 35.5, range 24–73). In contrast, IST in patients with rather moderate reduction of TCR V-beta diversity (n=4, CD8+ complexity scoring median 109.5, range 82–124) always failed (P=0.0095). If confirmed in a larger series of patients, TCR V-beta repertoire in BM may help to assign children with SAA up-front either to IST or to allogeneic stem-cell transplantation

Immunity and immunosuppression in experimental visceral leishmaniasis

Directory of Open Access Journals (Sweden)

Goto H.

2004-01-01

Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival

International Nuclear Information System (INIS)

Burkhardt, K.; Loughnan, M.S.; Diamantstein, T.; Mandel, T.E.

1988-01-01

Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes

Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

International Nuclear Information System (INIS)

Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

2014-01-01

Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

Predictors of mortality in patients with extensively drug-resistant Acinetobacter baumannii pneumonia receiving colistin therapy.

Science.gov (United States)

Choi, Ik Sung; Lee, Yu Ji; Wi, Yu Mi; Kwan, Byung Soo; Jung, Kae Hwa; Hong, Woong Pyo; Kim, June Myong

2016-08-01

The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

Science.gov (United States)

Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

2015-01-01

Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

Science.gov (United States)

Kawara, Fumiaki; Fujita, Tsuyoshi; Morita, Yoshinori; Uda, Atsushi; Masuda, Atsuhiro; Saito, Masaya; Ooi, Makoto; Ishida, Tsukasa; Kondo, Yasuyuki; Yoshida, Shiei; Okuno, Tatsuya; Yano, Yoshihiko; Yoshida, Masaru; Kutsumi, Hiromu; Hayakumo, Takanobu; Yamashita, Kazuhiko; Hirano, Takeshi; Hirai, Midori; Azuma, Takeshi

2017-03-21

To elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice. The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed. The FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Symptom Experience Associated With Immunosuppressive Medications in Chinese Kidney Transplant Recipients.

Science.gov (United States)

Teng, Sha; Zhang, Shuping; Zhang, Wenxin; Lin, Xiaohong; Shang, Yabin; Peng, Xiao; Liu, Hongxia

2015-09-01

Kidney transplant recipients require lifelong treatment with immunosuppressive medications to avoid graft rejection and graft loss. Symptoms experienced may influence recipients' perceived quality of life and medication adherence. The purpose of this study was to evaluate the symptom experience associated with immunosuppressive medications in adult kidney transplant recipients and to explore the association between the symptom experience and adherence to immunosuppressive medications. A cross-sectional design was used. The study was conducted in a general hospital in China from October 2013 to September 2014. A total of 231 recipients with a follow-up of at least 1 year after kidney transplantation were included. Symptom experience associated with immunosuppressive medications was measured by the 13-item Symptom Experience of Immunosuppressive-related Side Effects Scale. Self-reported adherence to immunosuppressive medications was assessed using the Adherence with Immunosuppressive Medication Scale. Ridit analysis was used to rank symptom distress items. A proportion of 60.6% of recipients were male; the time after kidney transplantation was arbitrarily divided into a short-term cohort (1-4 years) and a long-term cohort (4-16 years) according to the median duration of follow-up (4 years). High blood pressure, hair loss, and tiredness were the three most distressing symptoms over all items of the whole sample. High blood pressure was the most distressing symptom for the 1- to 4-year cohort and the 4- to 16-year cohort. For men high blood pressure was the most distressing symptom, whereas for women hair loss was the most distressing symptom. Recipients in the 4- to 16-year cohort perceived a higher level of symptom distress compared with those in the 1- to 4-year cohort, especially in excess hair growth and difficulty sleeping. A negative relationship was found between symptom distress and adherence to immunosuppressive medications (r = -.541, p = .000). Recipients

Oral candidiasis in immunosuppressed children and young adults after liver or kidney transplantation.

Science.gov (United States)

Olczak-Kowalczyk, Dorota; Pawłowska, Joanna; Garczewska, Barbara; Smirska, Ewa; Grenda, Ryszard; Syczewska, Małgorzata; Kowalczyk, Wojciech

2010-01-01

Candidiasis is an infectious complication in organ transplant recipients resulting from the patients' immunodeficiency and virulence of fungi pathogens. The purpose of this study was to evaluate the frequency of Candida spp. and identify their presence in the oral lesions of graft recipients. This study included 185 patients, 1.5 to 25.2 years of age (mean = 13.1 +/- 4.2 years) who were receiving combined immunosuppression treatment after kidney or liver transplantation and 70 control subjects. Evaluation included clinical oral examination, mycology, and statistical analysis. Candida spp. colonies were found in the oral mucosa of 63 (34%) graft recipients and in 19 (27%) control subjects. Candida albicans was the most prevalent species. This study showed that, regardless of the type of the organ transplant and immunosuppression, frequent, regular oral follow-up and mycologic tests are recommended. Diagnosing increased density of Candida spp. colonies in the oral cavity will help initiate early antifungal treatment. Candida spp. prevalence in the oral cavity in transplant recipients was higher than in immunocompetent control subjects. Kidney or liver transplantation predisposes one to the development of an increased density of Candida spp. colonies.

Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

Science.gov (United States)

Troncoso, P; Ortiz, A M; Jara, A; Vilches, S

2009-01-01

Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

Science.gov (United States)

Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

2017-08-01

ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10

Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential

OpenAIRE

Auletta, Jeffery J.; Zale, Elizabeth A.; Welter, Jean F.; Solchaga, Luis A.

2011-01-01

Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties that make them attractive therapeutic alternatives. We evaluated the in vitro immunosuppressive activity of medium conditioned by human MSCs from 5 donors expanded 13 passages with or without FGF-2. FGF-2 supplemen...

Does hormonal therapy influence sexual function in men receiving 3D conformal radiation therapy for prostate cancer?

International Nuclear Information System (INIS)

Chen, Christopher T.; Valicenti, Richard K.; Lu Jiandong; Derose, Troy; Dicker, Adam P.; Strup, Stephen E.; Mulholland, S. Grant; Hirsch, Irvin H.; McGinnis, David E.; Gomella, Leonard G.

2001-01-01

Purpose: We evaluated the effect of three-dimensional conformal radiation therapy (3D-CRT) with or without hormonal therapy (HT) on sexual function (SF) in prostate cancer patients whose SF was known before all treatment. Methods and Materials: Between March 1996 and March 1999, 144 patients received 3D-CRT (median dose = 70.2 Gy, range 66.6-79.2 Gy) for prostate cancer and had pre- and post-therapy SF data. All SF data were obtained with the O'Leary Brief SF Inventory, a self-administered, multidimensional, validated instrument. We defined total sexual potency as erections firm enough for penetration during intercourse. Mean follow-up time was 21 months (SD ± 11 months). The Wilcoxon signed-rank test was used to test for significance of the change from baseline. Results: Before 3D-CRT, 87 (60%) of 144 men were totally potent as compared to only 47 (47%) of 101 at 1-year follow-up. Of the 60 men totally potent at baseline and followed for at least 1 year, 35 (58%) remained totally potent. These changes corresponded to a significant reduction in SF (p<0.05). Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT (56% vs. 31%, p=0.012); however, they were also more likely to be potent at baseline (71% vs. 44%, p=0.001). Although these two groups had a significant reduction in SF from baseline, their change was not significantly different from each other. Conclusion: These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline. The addition of HT does not appear to increase the risk of sexual dysfunction

Radiation therapy

International Nuclear Information System (INIS)

Bader, J.L.; Glatstein, E.

1987-01-01

The radiation oncologist encounters the critically ill immunosuppressed patient in four settings. First, the newly diagnosed cancer patient presents for initial evaluation and treatment, with immunosuppression from the cancer itself, malnutrition, concomitant infectious disease, prior drug or alcohol abuse or other medical problems. Second, the previously treated cancer patient presents with metastatic or recurrent primary cancer causing local symptoms. Immune dysfunction in this setting may be due to prior chemotherapy and/or radiation as well as any of the original factors. Third, the patient previously treated with radiation presents with a life-threatening problem possibly due to complications of prior therapy. In this setting, the radiation oncologist is asked to evaluate the clinical problem and to suggest whether radiation might be causing part or all of the problem and what can be done to treat these sequelae of radiation. Fourth, the patient with a benign diagnosis (not cancer) is seen with a problem potentially emeliorated by radiation (e.g., kidney transplant rejection, preparation for transplant, or intractable rheumatoid arthritis). This chapter reviews these four issues and presents clinical and radiobiologic principles on which recommendations for therapy are based

The incidence of dysphagia in patients receiving cerebral reperfusion therapy poststroke.

Science.gov (United States)

Ribeiro, Priscila W; Cola, Paula C; Gatto, Ana R; da Silva, Roberta G; Luvizutto, Gustavo J; Braga, Gabriel P; Schelp, Arthur O; de Arruda Henry, Maria A C; Bazan, Rodrigo

2014-07-01

The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann-Whitney test and considered significant if P is less than .05. The moderate and severe degrees of dysphagia were more frequent (P=.013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P=.045). We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression

DEFF Research Database (Denmark)

Mocroft, Amanda; Bannister, Wendy P; Kirk, Ole

2012-01-01

The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression.......The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression....

Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

Energy Technology Data Exchange (ETDEWEB)

Lee, Won-Jae [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Hah, Young-Sool [Biomedical Research Institute, Gyeongsang National University Hospital, Jinju (Korea, Republic of); Ock, Sun-A. [Animal Biotechnology Division, National Institute of Animal Science, RDA, Suwon 441-706, Gyeonggi (Korea, Republic of); Lee, Jae-Hoon; Jeon, Ryong-Hoon; Park, Ji-Sung [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sang-Il [Department of Internal Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju (Korea, Republic of); Rho, Na-Young [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 4S7 (Canada); Rho, Gyu-Jin [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sung-Lim, E-mail: sllee@gnu.ac.kr [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of)

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.

What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

Science.gov (United States)

Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

2014-05-01

Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal

Bleeding-related admissions in patients with atrial fibrillation receiving antithrombotic therapy: results from the Tasmanian Atrial Fibrillation (TAF) study.

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Admassie, Endalkachew; Chalmers, Leanne; Bereznicki, Luke R

2017-12-01

Limited data are available from the Australian setting regarding bleeding in patients with atrial fibrillation (AF) receiving antithrombotic therapy. We aimed to investigate the incidence of hospital admissions due to bleeding and factors associated with bleeding in patients with AF who received antithrombotic therapy. A retrospective cohort study was conducted involving all patients with AF admitted to the Royal Hobart Hospital, Tasmania, Australia, between January 2011 and July 2015. Bleeding rates were calculated per 100 patient-years (PY) of follow-up, and multivariable modelling was used to identify predictors of bleeding. Of 2202 patients receiving antithrombotic therapy, 113 presented to the hospital with a major or minor bleeding event. These patients were older, had higher stroke and bleeding risk scores and were more often treated with warfarin and multiple antithrombotic therapies than patients who did not experience bleeding. The combined incidence of major and minor bleeding was significantly higher in warfarin- versus direct-acting oral anticoagulants (DOAC)- and antiplatelet-treated patients (4.1 vs 3.0 vs 1.2 per 100 PY, respectively; p = 0.002). Similarly, the rate of major bleeding was higher in patients who received warfarin than in the DOAC and antiplatelet cohorts (2.4 vs 0.4 vs 0.6 per 100 PY, respectively; p = 0.001). In multivariate analysis, increasing age, prior bleeding, warfarin and multiple antithrombotic therapies were independently associated with bleeding. The overall rate of bleeding in this cohort was low relative to similar observational studies. The rate of major bleeding was higher in patients prescribed warfarin compared to DOACs, with a similar rate of major bleeding for DOACs and antiplatelet agents. Our findings suggest potential to strategies to reduce bleeding include using DOACs in preference to warfarin, and avoiding multiple antithrombotic therapies in patients with AF.

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, M. Alma [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); and others

2015-05-01

Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed

Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies.

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Williams, AnnaLynn M; Baran, Andrea M; Meacham, Philip J; Feldman, Megan M; Valencia, Hugo E; Newsom-Stewart, Catherine; Gupta, Nealansh; Janelsins, Michelle C; Barr, Paul M; Zent, Clive S

2018-03-01

We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

Sarcoma de Kaposi em paciente transplantada renal em uso de Fk-506 Kaposi's Sarcoma in a renal transplant patient receiving Fk-506

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Jorge David Rocha Zanol

2002-12-01

Full Text Available O Sarcoma de Kaposi (SK é neoplasia maligna multicêntrica, cutânea e extracutânea, que tem sido descrita em pacientes transplantados renais que recebem terapia imunossupressora clássica. Este estudo descreve um caso de sarcoma de Kaposi em paciente transplantada renal recebendo FK-506, que surgiu 10 meses após o transplante.Kaposi's sarcoma is a cutaneous and extra cutaneous multicentric malignancy that has been widely described in renal-transplant patients under classic immunosuppressive therapy. This study describes a renal-transplant patient under immunosuppressive therapy with FK-506 who presented Kaposi's sarcoma 10 months after the transplantation.

Health care costs of adults treated for attention-deficit/hyperactivity disorder who received alternative drug therapies.

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Wu, Eric Q; Birnbaum, Howard G; Zhang, Huabin F; Ivanova, Jasmina I; Yang, Elaine; Mallet, David

2007-09-01

2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on

Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

Science.gov (United States)

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

Immunosuppression in the elderly renal allograft recipient

DEFF Research Database (Denmark)

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

2016-01-01

BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression...... strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus...... receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account...

CCL2 is critical for immunosuppression to promote cancer metastasis.

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Kudo-Saito, Chie; Shirako, Hiromi; Ohike, Misa; Tsukamoto, Nobuo; Kawakami, Yutaka

2013-04-01

We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail(+) tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail(+) tumor-derived CCL2 amplifies EMT events in other cells including Snail(-) tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail(+) tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4(+)FOXP3(+) Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail(+) tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail(+) tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator.

Science.gov (United States)

Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J; Jordaens, Luc; Pedersen, Susanne S

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD. Between 2003 and 2010, 448 consecutively implanted ICD patients were enrolled in the prospective Mood and personality as precipitants of arrhythmia in patients with an Implantable cardioverter Defibrillator: A prospective Study (MIDAS), of which 429 completed the Hospital Anxiety and Depression Scale (HADS) and the ICD Patient Concerns questionnaire (ICDC) at baseline. Eighty per cent of all patients received beta-blocker therapy. In univariate analysis, beta-blocker therapy was not significantly associated with symptoms of anxiety, depression, and ICD concerns (β = -0.030, β = 0.007, and β = -0.045, respectively; all P's >0.36). Type of beta-blocker showed a trend towards significance for mean levels of ICD concerns (P = 0.09). No association was found between dosage and emotional distress (all P's >0.21). After adjustment for relevant clinical and demographic variables, the association of beta-blocker therapy and symptoms of anxiety, depression, and ICD concerns remained non-significant (β = 0.009, β = 0.037, and β = 0.019, respectively; all P's >0.47). In patients receiving an ICD, beta-blocker therapy was not associated with symptoms of anxiety, depression, and ICD concerns. Research is warranted that further elucidates the link between beta-blocker therapy and emotional distress in this vulnerable patient group.

Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

Institute of Scientific and Technical Information of China (English)

Rita Diehl; Fabienne Ferrara; Claudia Müller; Antje Y Dreyer; Damian D McLeod; Stephan Fricke; Johannes Boltze

2017-01-01

Almost every experimental treatment strategy using non-autologous cell,tissue or organ transplantation is tested in small and large animal models before clinical translation.Because these strategies require immunosuppression in most cases,immunosuppressive protocols are a key element in transplantation experiments.However,standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species.Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation.This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects.It also summarizes contemporary knowledge of novel immunomodulatory strategies,such as the use of mesenchymal stem cells or antibodies.Thus,this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

UVB-induced systemic immunosuppression: role of mast cells and histamine

International Nuclear Information System (INIS)

Hart, P.H.; Grimbaldeston, M.A.; Finlay-Jones, J.J.

1999-01-01

Full text: UVB radiation (290-320 nm) is immunosuppressive by multiple mechanisms allowing the outgrowth of UV-induced tumours in both mouse and man. Furthermore, patients with non-melanoma skin cancers have a higher risk of death from other cancers which could be explained by UV-induced immunomodulation. The mechanism(s) of suppression by UVB depend on whether the sensitising antigen is applied to the irradiated site ('local') or to non-irradiated sites ('systemic'). In the former, the activity of UV-induced TNFα is important as it affects the migration of Langerhans cells to draining lymph nodes. In contrast, histamine from dermal mast cells is critical to the early events by which UVB can suppress systemic immune responses. The prevalence of dermal mast cells in 7 strains and substrains of mice correlates directly with their susceptibility to UVB-induced systemic immunosuppression. Furthermore, mast cell depleted mice (Wf/Wf) are resistant to UVB-induced systemic immunomodulation. However, they become susceptible after reconstitution of the site to be irradiated with bone marrow derived mast cell precursors. The mice also gain susceptibility to cis-urocanic acid-induced systemic immunomodulation. There is considerable evidence that histamine is the mast cell product critical to downstream immunosuppressive events. Firstly, physiological concentrations of histamine suppress contact hypersensitivity responses. Secondly, histamine receptor antagonists halve UVB-induced systemic immunosuppression. Thirdly, mice with different UVB-susceptibilities are equally susceptible to histamine-induced immunosuppression, and finally, histamine can suppress contact hypersensitivity responses in Wf/Wf mice. We suggest that histamine may be immunomodulatory by multiple pathways. Histamine can induce the production of immunosuppressive prostanoids from keratinocytes. A lymphocyte-derived, histamine-induced suppressor factor was reported in the 1970's. More recently histamine has

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

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Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

2015-01-01

Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Prevention and treatment of Encephalitozoon cuniculi infection in immunosuppressed rabbits with fenbendazole.

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Abu-Akkada, S S; Oda, S S

2016-01-01

This study was conducted to evaluate the efficacy of oral administration of fenbendazole (20 mg/kg body weight) prior to and after experimental infection of immunosuppressed rabbits with Encephalitozoon cuniculi . A total of thirty rabbits were divided into five groups: NN (non-immunosuppressed; non-infected), IN (immunosuppressed; non-infected), IPI (immunosuppressed; protected-infected), ITI (immunosuppressed; treated-infected), and II (immunosuppressed; infected) groups. Fenbendazole was administered as a prophylactic for seven successive days before infection with E. cuniculi and as a treatment for four weeks initiated on the 28th day post-challenge (PC). Experimental rabbits were infected with intraperitoneal injection of 2 × 10 5 E. cuniculi spores. Parameters evaluated were body weight, detection of spores in urine, serum antibody assay, hematological, biochemical and histopathological changes. The IPI and ITI groups showed a significant better final bwt than the II group. Spores were detected in urine of all infected rabbits from the 28th day PC until the end of the study. The IPI group showed the least values of antibodies (IgG) compared to the ITI and II groups. Concerning histopathological changes, the intensity of the lesions was marked particularly in the II rabbits and to a lesser extent in the ITI rabbits. Noticeable improvement was found in the IPI rabbits. It could be concluded that fenbendazole was effective to some extent in protection of rabbits against E. cuniculi infection, while when administered as a therapeutic no significant effects were observed.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe

DEFF Research Database (Denmark)

Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein

2017-01-01

HR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate......BACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted...... patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (a...

Dominican Children with HIV Not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development

Directory of Open Access Journals (Sweden)

Maria Hernandez-Reif

2008-01-01

Full Text Available Forty-eight children (M age = 4.8 years infected with HIV/AIDS and living in the Dominican Republic were randomly assigned to a massage therapy or a play session control group. The children in the massage therapy group received two weekly 20-min massages for 12 weeks; the children in the control group participated in a play session (coloring, playing with blocks for the same duration and length as the massage therapy group. Overall, the children in the massage therapy group improved in self-help abilities and communication, suggesting that massage therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the HIV infected children who were six or older also showed a decrease in internalizing behaviors; specifically depressive/anxious behaviors and negative thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence below normal functioning for 70% of the HIV infected children and very high incidences of mood problems (depression, withdrawn for 40% of the children and anxiety problems for 20% of the children, suggesting the need for better monitoring and alternative interventions in countries with limited resources to improve cognition and the mental health status of children infected with HIV/AIDS.

[The variation and clinical significance of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia before and after immunosuppressive therapy].

Science.gov (United States)

Sun, Ying-xin; Zhu, Ming-qing; He, Guang-sheng; Wang, Xiu-li; Fang, Bao-zhi; Lu, Cong; Liu, Zhen-zhen; Wu, Qian; Yang, Yong; Wu, De-pei; Sun, Ai-ning

2013-07-01

To evaluate the evolution of paroxysmal nocturnal hemoglobinuria (PNH) clone and its clinical significance before and after immunosuppressive therapy (IST) in patients with aplastic anemia (AA). A total of 186 patients diagnosed as AA were enrolled in this study. Among them, 55 patients were diagnosed as severe AA (SAA) and treated with cyclosporine (CsA) plus anti-thymocyte globulin (ATG), 131 were diagnosed as non SAA (NSAA) and treated with CsA alone. All patients were screened for PNH clone by flow cytometry before treatment and followed up for 18-76 months, with a median time of 22 months. Positive PNH clones were detected in 10 SAA (18.9%) patients, significantly more than that of NSAA group [9 patients (7.4%), t = 5.041, P = 0.025]. The proportions of PNH clones in SAA group at 6, 12, 24 and > 24 months were 13.38%, 14.88%, 20.00% and 18.85%, respectively, also significantly higher than those of NSAA patients (5.67%, 5.31%, 5.47% and 9.08%, all P values clone was positive or negative. PNH clone are detectable in AA patients either treated with ATG plus CsA or CsA alone, and more significant by ATG plus CsA. Whether PNH clone occurred before or after IST does not affect the therapeutic efficacy.

Perspectives of newly diagnosed advanced cancer patients receiving dignity therapy during cancer treatment.

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Dose, Ann Marie; Rhudy, Lori M

2018-01-01

Dignity therapy is a psychosocial intervention that has been used primarily at the end of life to improve quality of life and other patient outcomes, but many individuals are unable to complete it due to health decline and death. The purpose of this study was to identify what individuals with advanced pancreatic or lung cancer with limited life expectancy, undergoing active cancer treatment describe during the dignity therapy intervention as important to them when not immediately facing end of life. Twenty patients undergoing chemotherapy for advanced cancer participated in a dignity therapy intervention study. Initial interviews were analyzed using descriptive content analysis. Family provided the overall context and background for emerging themes of defining events, accomplishments, and God's plan, which led to lessons learned, and resulted in messages of hope. Interviews were often autobiographical in nature and contained much reminiscence, consistent with dignity therapy's intent. Few participants spoke about their cancer diagnoses during the interview. This study adds unique insight into the use of dignity therapy for those still receiving active cancer treatment, different from work by others in which it was offered only at end of life. As part of supportive care, clinicians need to validate the importance of family to those with advanced cancer and to provide opportunities for patients to share what they have learned throughout life and to impart messages of hope to those closest to them.

Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo.

Science.gov (United States)

Larsabal, Maiana; Marti, Aurélie; Jacquemin, Clément; Rambert, Jérôme; Thiolat, Denis; Dousset, Léa; Taieb, Alain; Dutriaux, Caroline; Prey, Sorilla; Boniface, Katia; Seneschal, Julien

2017-05-01

The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the vitiligo group. All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to vitiligo, patients receiving anti-PD-1 therapies who developed vitiligo-like lesions did not report any personal or family histories of vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-γ and tumor necrosis factor-alfa. This cross-sectional study concerned a single center. Clinical and biological patterns of vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from vitiligo, suggesting a different mechanism. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Use of High-Flow Nasal Cannula Oxygen Therapy in a Pregnant Woman with Dermatomyositis-Related Interstitial Pneumonia

Directory of Open Access Journals (Sweden)

Tomohiro Shoji

2017-01-01

Full Text Available A 33-year-old pregnant woman was referred to our hospital with respiratory distress at 30 weeks of gestation. Chest computed tomography (CT scans revealed pulmonary infiltrates along the bronchovascular bundles and ground-glass opacities in both lungs. Despite immediate treatment with steroid pulse therapy for suspected interstitial pneumonia, the patient’s condition worsened. Respiratory distress was slightly alleviated after the initiation of high-flow nasal cannula (HFNC oxygen therapy (40 L/min, FiO2 40%. We suspected clinically amyopathic dermatomyositis (CADM complicating rapidly progressive refractory interstitial pneumonia. In order to save the life of the patient, the use of combination therapy with immunosuppressants was necessary. The patient underwent emergency cesarean section and was immediately treated with immunosuppressants while continuing HFNC oxygen therapy. The neonate was treated in the neonatal intensive care unit. The patient’s condition improved after 7 days of hospitalization; by this time, she was positive for myositis-specific autoantibodies and was diagnosed with interstitial pneumonia preceding dermatomyositis. This condition can be potentially fatal within a few months of onset and therefore requires early combination immunosuppressive therapy. This case demonstrates the usefulness of HFNC oxygen therapy for respiratory management as it negates the need for intubation and allows for various treatments to be quickly performed.

DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

Science.gov (United States)

Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

2017-01-01

The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe - a Hungarian nationwide observational study

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Simon László

2009-09-01

Full Text Available Abstract Background Infliximab (IFX has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohn's disease (CD, with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary. Methods During a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6 at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy. Results Three hundred and sixty three patients (183 women and 180 men were treated with IFX since 2000. Mean age was 33.5 ± 11.2 years and the mean duration of disease was 6.7 ± 6.1 years. The population included 114 patients (31.4% with therapy-refractory CD, 195 patients (53.7% with fistulas, 16 patients (4.4% with both therapy-refractory CD and fistulas, and 26 patients (7.2% with steroid dependent CD. Overall response rate was 86.2% (313/363. A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99 and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596. Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%, 17 delayed type hypersensitivity (4.7%, 16 infections (4.4%, and 3 malignancies (0.8%. Conclusion IFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

Endogenous Nocardial Endophthalmitis in an Immunosuppressed Patient: A Serious Warning of an Underlying Life Threatening and Blinding Disorder.

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Trehan, Hemant; Kaushik, Jaya; Jain, Vaibhav Kumar; Parihar, Jitendra Kumar Singh; Avasthi, Abhijit

2017-01-01

To report a case of bilateral endogenous nocardial endophthalmitis with central nervous system involvement in an immunocompromised individual with an extremely poor outcome. A 35-year-old man with a history of long-term, prescribed oral steroid use for membranoproliferative glomerulonephritis presented with profound bilateral vision loss. Patient's diagnosis of bilateral endogenous nocardial endophthalmitis was delayed. Nocardia was finally isolated from a brain biopsy after a repeat magnetic resonance imaging revealed a brain abscess. With anti-nocardia therapy, patient improved systemically, but the visual outcome was poor, with no light perception in both eyes. Ocular nocardiosis is a serious vision and life threatening disorder, particularly in patients on immunosuppressive therapy. A high index of suspicion is required for successful treatment.

Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review.

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Streed, Carl G; Harfouch, Omar; Marvel, Francoise; Blumenthal, Roger S; Martin, Seth S; Mukherjee, Monica

2017-08-15

Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.

Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

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Muccioli Cristina

2002-01-01

Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

Frequency, predictors, and consequences of maintenance infliximab therapy intensification in ulcerative colitis

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Luis Fernández-Salazar

2015-09-01

Full Text Available Introduction: Infliximab (IFX therapy intensification in ulcerative colitis (UC is more common than established in pivotal studies. Objectives: To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. Methods: A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. Results: Follow-up time from induction to data collection: 38 months [interquartile range (IQR, 20-62]. Time on IFX therapy: 24 months (IQR, 10-44. In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002, steroid reintroduction (35% vs. 18%; p, 0.018, and colectomy (22% vs. 6.4%; p, 0.011 were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks. Conclusions: Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predicts non-intensification. Intensification, while effective, is associated with poorer outcome.

Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report

OpenAIRE

ZHAO, QIONG; WANG, YINA; TANG, YEMIN; PENG, LING

2013-01-01

As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An ...

Rethinking the role of myeloid-derived suppressor cells in adoptive T-cell therapy for cancer

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Arina, Ainhoa

2014-01-01

The expansion of cancer-induced myeloid cells is thought to be one of the main obstacles to successful immunotherapy. Nevertheless, in murine tumors undergoing immune-mediated destruction by adoptively transferred T cells, we have recently shown that such cells maintain their immunosuppressive properties. Therefore, adoptive T-cell therapy can, under certain conditions, overcome myeloid cell immunosuppression. PMID:25050213

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy

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Megan E. Kunka

2015-01-01

Full Text Available Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours, which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient’s actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Cognitive Behavioral Therapy for Psychosis (CBT-p) Delivered in a Community Mental Health Setting: A Case Comparison of Clients Receiving CBT Informed Strategies by Case Managers Prior to Therapy.

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Sivec, Harry J; Montesano, Vicki L; Skubby, David; Knepp, Kristen A; Munetz, Mark R

2017-02-01

This exploratory case comparison examines the influence of case management activities on engagement and progress in psychotherapy for clients with schizophrenia. Six clients were recruited to participate in ten sessions of Cognitive Behavioral Therapy for psychosis (CBT-p). Three clients who had received Cognitive Behavioral techniques for psychosis (CBt-p, a low-intensity case management intervention) prior to receiving therapy were selected from referrals. A comparison group of three clients who had received standard case management services was selected from referrals. Cases within and across groups were compared on outcome measures and observations from case review were offered to inform future research. Delivering CBT-p services on a continuum from low- to high-intensity is discussed.

Immunosuppression and tolerance after total lymphoid irradiation (TLI)

International Nuclear Information System (INIS)

Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

1980-01-01

The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

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Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

2014-01-01

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

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Zhao, Chan; Zhang, Meifen

2017-04-10

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and

Is exercise training safe and beneficial in patients receiving left ventricular assist device therapy?

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Alsara, Osama; Perez-Terzic, Carmen; Squires, Ray W; Dandamudi, Sanjay; Miranda, William R; Park, Soon J; Thomas, Randal J

2014-01-01

Because a limited number of patients receive heart transplantation, alternative therapies, such as left ventricular assist device (LVAD) therapy, have emerged. Published studies have shown that LVAD implantation, by itself, improves exercise tolerance to the point where it is comparable to those with mild heart failure. The improvement in exercise capacity is maximally achieved 12 weeks after LVAD therapy and can continue even after explantation of the device. This effect varies, depending on the type of LVAD and exercise training. The available data in the literature on safety and benefits of exercise training in patients after LVAD implantation are limited, but the data that are available suggest that training trends to be safe and have an impact on exercise capacity in LVAD patients. Although no studies were identified on the role of cardiac rehabilitation programs in the management of LVAD patients, it appears that cardiac rehabilitation programs offer an ideal setting for the provision of supervised exercise training in this patient group.

Follow up of Crohn's disease under therapy with hydro-MRI

International Nuclear Information System (INIS)

Ganten, M.; Flosdorff, P.; Grueber-Hoffmann, B.; Erb, G.; Hansmann, J.; Encke, J.

2003-01-01

Evaluation of typical MRI-findings in patients with Crohn's disease receiving therapy.Correlation with the course of disease.Patients and methods 81 follow-up MRI-studies in 25 patients conducted within a period of 3 weeks to 4 years were evaluated retrospectively.Therapy consisted in various combinations of antibiotics and immunosuppressive agents and if necessary operation. The findings of the MRI-studies were correlated with clinical data (e.g.operation of Crohn's complications) and the subjective perception during therapy. The morphological substrate of Crohn's disease in the Hydro-MRI images is reliably detected. Especially in a delineation of extraluminal changes MRI is superior to endoscopy and enteroclysis.Independent from clinical symptoms short- and middleterm follow-up showed inflammatory changes of the intestinal wall in all 25 patients. In 24/81 studies there was persistence or even progression of Crohn's disease in the MRI-studies, although patients were free of symptoms by the time of image acquisition. Hydro-MRI is a modality for the evaluation of inflammatory changes in patients with Crohn's disease.Independent from clinical symptoms persistence of Crohn's disease is detectable. (orig.) [de

Malfunctions of Implantable Cardiac Devices in Patients Receiving Proton Beam Therapy: Incidence and Predictors

International Nuclear Information System (INIS)

Gomez, Daniel R.; Poenisch, Falk; Pinnix, Chelsea C.; Sheu, Tommy; Chang, Joe Y.; Memon, Nada; Mohan, Radhe; Rozner, Marc A.; Dougherty, Anne H.

2013-01-01

Purpose: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. Methods and Materials: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. Results: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. Conclusions: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving

Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels

DEFF Research Database (Denmark)

Kamara, David A; Smith, Colette; Ryom, Lene

2016-01-01

BACKGROUND: Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear......%, 92% and 80% contributed at least one TG/TC/HDL-C measurement (median follow-up 6.8, 6.8 and 5.0 years, respectively). Predicted mean (95% CI) baseline levels for TG, TC and HDL-C (mmol/l), were 2.10 (2.05, 2.14), 4.94 (4.91, 4.98) and 1.08 (1.07, 1.10), respectively. Lopinavir was associated...... with the worst TG profile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared with emtricitabine/tenofovir, whereas...

The use of immunosuppressive agents in the management of recalcitrant lower limb ulcers.

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Millen, A; Coulston, J; Brennan, J; Kennedy, T

2014-08-01

Lower limb ulcers that are resistant to standard forms of treatment place a significant burden on both patients and health services. There is no widely agreed definition of a recalcitrant ulcer but failure to heal following 6-12 months of focused treatment would identify a small group of patients with highly resistant ulceration. We describe a series of patients with recalcitrant ulceration for which immunosuppressive agents have been used. This is a case series of 13 patients who underwent immunomodulation therapy for lower limb ulcers at a tertiary referral university hospital. Regimens of immunomodulation used mainly ciclosporin and/or cyclophosphamide, with concurrent antibiotic therapy. Case notes and computer systems were analysed by two reviewers. A patient was deemed to have a success if their ulcer fully healed while on immunomodulation therapy. Over a period of eight years, from 2004-2012, 13 patients underwent immunomodulation therapy. Among these patients there were 18 ulcerated limbs. Ulcer healing occurred in 10 limbs out of 18 (55.6%) and full healing occurred in six patients (46.2%). Ulcers were present for a median of five years (range 2-40 years), with a median diameter of 7.5 cm (range 4-18 cm) before treatment. Treatment of truly recalcitrant ulceration can be very frustrating for both the patient and physician, with poor success from more standard forms of treatment. We report experience with immunomodulation therapy that suggests there may be benefit from using this treatment in a subset of patients with this debilitating disease.

Thorax irradiation triggers a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells

International Nuclear Information System (INIS)

Wirsdörfer, Florian; Cappuccini, Federica; Niazman, Muska; Leve, Simone de; Westendorf, Astrid M; Lüdemann, Lutz; Stuschke, Martin; Jendrossek, Verena

2014-01-01

Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but their contribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on the T cell compartment with a focus on immunosuppressive regulatory T cells (Treg). C57BL/6 wild type mice (WT) received anesthesia only (sham controls, 0 Gy) or were exposed to a single dose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes were collected 10 to 84 days post-irradiation and phenotypically characterized by flow cytometry. Whole thorax irradiation provoked an increased influx of CD3+ T cells at 42 and 84 days post-irradiation. In contrast, local irradiation caused a sustained reduction in CD3+ T cells in peripheral lymphoid tissues. Interestingly, we observed a significant local and systemic increase in the fraction of CD4+ T cells expressing the transcription factor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulation of Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment and immunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able to suppress CD4+ effector T cells to a similar extent as Treg isolated from control mice. The response of the adaptive immune system to whole thorax irradiation is characterized by local immunoactivation and systemic immunosuppression. The transient accumulation of immunosuppressive CD4+ FoxP3+ Treg may be required to protect the lung against excessive inflammation-induced tissue damage. Further investigations shall define the mechanisms underlying the accumulation of Treg and their role for the pathogenesis of radiation-induced lung disease

Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa

NARCIS (Netherlands)

Mekuria, Legese A.; Sprangers, Mirjam A. G.; Prins, Jan M.; Yalew, Alemayehu W.; Nieuwkerk, Pythia T.

2015-01-01

Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify

Reactivation of Cutaneous Leishmaniasis after Renal Transplantation: A Case Report

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Hossein Mortazavi

2014-01-01

Full Text Available A 45-year-old man with reactivation of previously existing and subsiding cutaneous leishmaniasis on his wrist and lower leg (shin after renal transplantation was admitted to our dermatology service on March 2008. He presented to us with two huge tumoral and cauliflower-like lesions. Skin smear and histopathology of skin showed leishman bodies and confirmed the diagnosis. After renal transplantation, he received cyclosporine plus prednisolone to induce immunosuppression and reduce the probability of transplant rejection. After immunosuppressive therapy, reactivation of cutaneous leishmaniasis with the above presentation took place. The patient responded to 800 mg/day intravenous sodium stibogluconate for 3 weeks plus local cryotherapy. Systemic plus local therapy along with reducing the doses of immunosuppressive drugs led to improvement of lesions. Reactivation of leishmaniasis after immunosuppression has been rarely reported.

The targeting of immunosuppressive mechanisms in hematological malignancies

DEFF Research Database (Denmark)

Andersen, M H

2014-01-01

enzymes such as indoeamine-2,3-dioxygenase (IDO). The possible therapeutic targeting of these pathways is also discussed. Exciting new strategies that might affect future antileukemia immunotherapy include monoclonal antibodies that block inhibitory T-cell pathways (PD-1/PD-L1) and the prevention...... of tryptophan depletion by IDO inhibitors. Furthermore, the clinical effect of several chemotherapeutic drugs may arise from the targeting of immunosuppressive cells. Evidence for a new feedback mechanism to suppress the function of regulatory immune cells was recently provided by the identification...... and characterization of spontaneous cytotoxic T lymphocyte (CTL) responses against regulatory immune cells. Such specific CTLs may be immensely useful in anticancer immunotherapy (for example, by anticancer vaccination). The targeting of one or more immunosuppressive pathways may be especially interesting...

Neurologic emergencies in HIV-negative immunosuppressed patients.

Science.gov (United States)

Guzmán-De-Villoria, J A; Fernández-García, P; Borrego-Ruiz, P J

HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

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Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2014-03-01

Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

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Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

2008-01-01

CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

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Sandra López-Verdín

2013-01-01

Full Text Available Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV, and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow.

Immunosuppressive potential of bardoxolone methyl using a modified murine local lymph node assay (LLNA).

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Kitsukawa, Mika; Tsuchiyama, Hiromi; Maeda, Akihisa; Oshida, Keiyu; Miyamoto, Yohei

2014-08-01

2-Cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl) is one of the synthetic oleanane triterpenoids (SOs). It is known that it is the strongest Nrf2/ARE signaling inducer of SOs and slightly inhibits immune response. Little was known about the immunomodulatory action of CDDO-Me in vivo. We assessed its immunosuppressive potential by using the modified mouse lymph node assay (LLNA) including immunosuppression-related gene expression analysis. In the modified LLNA, CDDO-Me showed a significant decrease in lymph node weight and changes in expressions of the immunosuppression-related genes, Zfp459 and Fmo2. It has been already reported that a decrease in lymph node weight was induced by several types of immunosuppressive chemicals such as calcineurin inhibitors, antimetabolites, steroids, and alkylators. In addition, changes in Zfp459 and Fmo2 expression was reported in response after only treatment of antimetabolites. From these results, CDDO-Me is considered to have an immunosuppressive action and similar mechanism to antimetabolites.

Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

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Elena Crespo

Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

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Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

2018-04-07

Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cryptococcus laurentii fungaemia in a cervical cancer patient

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Rejane Pereira Neves

2015-11-01

Full Text Available Infections caused by emerging Cryptococcus non-neoformans species are being reported with increasingly frequency. Here, we present a case of fungaemia by Cryptococcus laurentii in a woman receiving aggressive immunosuppressive therapy for cervical neoplasia. Three venous blood samples were aseptically collected on consecutive days and C. laurentii was isolated and identified through phenotypic and molecular methods. After central venous catheter removal and appropriate antifungal therapy, the patient showed significant improvement and blood culture became negative. Thus, patients following immunosuppressive therapies and using invasive medical devices are at risk of C. laurentii blood infections.

Virtual reality-based therapy for the treatment of balance deficits in patients receiving inpatient rehabilitation for traumatic brain injury.

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Cuthbert, Jeffrey P; Staniszewski, Kristi; Hays, Kaitlin; Gerber, Don; Natale, Audrey; O'Dell, Denise

2014-01-01

To evaluate the feasibility and safety of utilizing a commercially available virtual reality gaming system as a treatment intervention for balance training. A randomized controlled trial in which assessment and analysis were blinded. An inpatient rehabilitation facility. Interventions included balance-based physical therapy using a Nintendo Wii, as monitored by a physical therapist, and receipt of one-on-one balance-based physical therapy using standard physical therapy modalities available for use in the therapy gym. Participants in the standard physical therapy group were found to have slightly higher enjoyment at mid-intervention, while those receiving the virtual reality-based balance intervention were found to have higher enjoyment at study completion. Both groups demonstrated improved static and dynamic balance over the course of the study, with no significant differences between groups. Correlational analyses suggest a relationship exists between Wii balance board game scores and BBS scores for measures taken beyond the baseline assessment. This study provides a modest level of evidence to support using commercially available VR gaming systems for the treatment of balance deficits in patients with a primary diagnosis of TBI receiving inpatient rehabilitation. Additional research of these types of interventions for the treatment of balance deficits is warranted.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

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Kumari, P; Nigam, R; Singh, A; Nakade, U P; Sharma, A; Garg, S K; Singh, S K

2017-09-01

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro.

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Martina, M N; Ramirez Bajo, M J; Bañon-Maneus, E; Moya Rull, D; Hierro-Garcia, N; Revuelta, I; Campistol, J M; Rovira, J; Diekmann, F

2016-11-01

Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27 + CD24 + phenotype was not modified by any immunosuppressive treatment. Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation. Copyright © 2016. Published by Elsevier Inc.

ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.

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Kim, Min Jeong; Tsinalis, Dimitrios; Franz, Stefan; Binet, Isabelle; Gürke, Lorenz; Mihatsch, Michael J; Steiger, Jürg; Thiel, Gilbert; Dickenmann, Michael

2008-01-01

Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible. Immunologically high risk kidney recipients with CDC-PRA ł 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group. The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient. In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.

Accuracy of C - Reactive protein as a bacterial infection marker in critically immunosuppressed patients: A systematic review and meta-analysis.

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de Oliveira, Vanessa Martins; Moraes, Rafael Barberena; Stein, Airton Tetelbom; Wendland, Eliana Márcia

2017-12-01

There is a need for a better understanding of the role of C-reactive protein (CRP) as a valid marker for the detection of bacterial infections in critically immunosuppressed patients. A high negative predictive value of CRP is also needed to rule out sepsis and bacterial infections in immunocompetent patients. However, few studies have evaluated the performance of CRP in immunocompromised hosts. The aim of the present study was to evaluate the performance of CRP as a marker of infection in critically immunosuppressed patients. The inclusion criterion was immunosuppression for which CRP was used as a bacterial infection marker. Searches were performed in the Cochrane Register, MEDLINE, EMBASE, SCOPUS, Web OF Science, LILACS and CINAHL databases. We applied the Quality Assessment of Diagnostic Accuracy Studies tool 2 (QUADAS 2) to evaluate the quality of the articles and evaluated the test accuracy parameters using hierarchical summary receiver operating characteristic (HSROC) curves and bivariate random effect models. Only 13 of 21 studies produced quantitative results. We analyzed all studies using the random effects method (restricted maximum likelihood) and obtained a joint diagnostic odds ratio (DOR) of 3.04 (95% confidence interval [CI] 1.71-5.40) with heterogeneity (I 2 =91%, Q=181.48, p<0.001). Therefore, a bivariate model was applied. Analyzing the tuberculosis carrier, steroid user, or presence of opportunistic infection subgroups, as described in the proposal, was not possible due to the lack of information on these topics included in the articles. CRP appears to be a good screening tool for sepsis in critically immunosuppressed patients. Submitted PROSPERO 2015: CRD42015019329. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients.

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Fairfield, Cameron; Penninga, Luit; Powell, James; Harrison, Ewen M; Wigmore, Stephen J

2018-04-09

Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017. Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed-effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a

Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system.

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de Boysson, Hubert; Parienti, Jean-Jacques; Arquizan, Caroline; Boulouis, Grégoire; Gaillard, Nicolas; Régent, Alexis; Néel, Antoine; Detante, Olivier; Touzé, Emanuel; Aouba, Achille; Bienvenu, Boris; Guillevin, Loïc; Naggara, Olivier; Zuber, Mathieu; Pagnoux, Christian

2017-10-01

We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

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Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

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E. A. Starikova

2015-01-01

Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy

DEFF Research Database (Denmark)

Ostrowski, Sisse R; Katzenstein, Terese L; Thim, Per T.

2005-01-01

Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined....

Recent advances in cell-based therapy for Parkinson disease

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Astradsson, Arnar; Cooper, Oliver; Vinuela, Angel

2008-01-01

In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression...

Pulmonary tuberculosis in a patient with rheumatoid arthritis undergoig immunosuppressive treatment: case report

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Sandro Ceratti

2014-02-01

Full Text Available Rheumatoid arthritis is a disease which characteristically affects the joints. Because it is an autoimmune disease, immunosuppressive drugs are widely used in its treatment. The present case report illustrates the association of immunosuppressive treatment with the development of opportunistic infections in a 64-year-old patient.

A systematic checklist approach to immunosuppression risk management: An audit of practice at two clinical neuroimmunology centers.

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Mori, Amelia M; Agarwal, Smriti; Lee, Monique W M; Rafferty, Martina; Hardy, Todd A; Coles, Alasdair; Reddel, Stephen W; Riminton, D Sean

2017-11-15

There is no consensus approach to safety screening for immune intervention in clinical neuroimmunology. An immunosuppression risk evaluation checklist was used as an audit tool to assess real-world immunosuppression risk management and formulate recommendations for quality improvements in patient safety. Ninety-nine patients from two centres with 27 non-MS diagnoses were included. An average of 1.9 comorbidities with the potential to adversely impact morbidity and mortality associated with immunosuppression were identified. Diabetes and smoking were the most common, however a range of rarer but potentially life-threatening co-morbid disorders in the context of immunosuppression were identified. Inadequate documentation of risk mitigation tasks was common at 40.1% of total tasks across both cohorts. A routine, systematic immunosuppression checklist approach should be considered to improve immunosuppression risk management in clinical neuroimmunology practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

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Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE

The Immunosuppressant Effect Comparation Between Ethyl Acetate and n-Butanol Fractions of Kalanchoe Pinnata (Lmk Pers In 2,6,10,14 Tetramethylpentadecane-Treated Mice

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Niken Indriyanti

2017-07-01

Full Text Available Immunosuppressant drugs are the main treatment of lupus patient. The ACR and SLICC treatment guidelines are able to increase the quality of life, but the outcome is not satisfying since the off-label therapy of corticosteroids and cytotoxic drugs give a lot of side effects. Many breakthrough efforts still develop in order to find the safe and effective drugs for lupus, such as finding immunosuppressant drugs from natural resources. One of the potential resources is Kalanchoe pinnata (Lmk Pers, which have immunosuppressant, anti-inflammatory, antinociceptive, and antioxidant effects. Thus, in the previous study, we found the effect of the aqueous extract of Kalanchoe pinnata (Lmk Pers is active to repair the lupus manifestation in 2,6,10,14 tetramethylpentadecane (TMPD-treated mice. Then, this research was focused on the in vivo immunosuppressant effect of a flavonoid-rich fraction of the extract which was consisted of the ethyl acetate (FE and n-butanol (FB fractions. The induction method and the extraction procedure were the same as the previous study and then the fractionation was performed by using liquid-liquid extraction. After 2-week treatment of both fractions, we obtained the differences in the total leukocytes, organ indexes, and also the spleen, kidney, and joint structure parameters. The total leukocyte of the FE group was 3,600±264 cells/mm3, which was lower than that in the FB group. The spleen and kidney indexes increased after the administration of FB fraction, while the FE fraction was not. At last, despite the histology observation of spleen resembled mild structural changes differences, the clear differences between both treatment groups occurred in the kidney and joint histology. The differences led to a conclusion that the FE fraction has the better immunosuppressant effect in TMPD-treated mice.

Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation.

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Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Pascher, Andreas; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Brockmann, Jens; Andrassy, Joachim; Banas, Bernhard; Jauch, Karl-Walter

2012-04-01

Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

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Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J

2012-01-01

Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We...... investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD....

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

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Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

2012-01-01

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

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Xiaojie Wang

2015-01-01

Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

Retrospective chart review of elderly patients receiving electroconvulsive therapy in a tertiary general hospital

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Mosam Phirke; Harshal Sathe; Nilesh Shah; Sushma Sonavane; Anup Bharati; Avinash DeSousa

2015-01-01

Background: Electroconvulsive therapy (ECT) is the one of the oldest and effective treatments in psychiatry today. It has been used in a wide variety of psychiatric disorders in both young and old patients. Aims of the study: The present study is a retrospective chart review of geriatric patients receiving ECT as a treatment option in a tertiary care general hospital psychiatry setting. Methodology: The study evaluated ECT records over a 5-year period between the years 2010 and 2014...

Reasons for not receiving thrombolytic therapy in patients with acute myocardial infarction admitted to Bu-Ali Sina Hospital in Qazvin (2013-14

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MM. Daei

2017-04-01

Full Text Available This hospital-based cross-sectional study was conducted in 2013-14 in Qazvin Bu-Ali Sina Hospital. 170 patients with acute myocardial infarction who not receiving thrombolytic therapy entered the study and were analyzed. Medical history, physical examination, twelve lead ECG and cardiac biomarkers were obtained. The mean age of the patients was 63.4±14.4 years (from 19 to 90 years. 110 (64.7% of the patients were male and 48 (28.2% were diabetic. 86 (50% of patients due to late presentation and 47 (28% due to lack of diagnosis and 29 (17% due to contraindication and 8 (5% due to autolysis or coronary spam were not received thrombolytic therapy. We could reduce failure of receiving thrombolytic therapy more than seventy five percent with increasing people's awareness about the symptoms of myocardial infarction and skills of health staff in relation to the proper and timely diagnosis of myocardial infarction.

Impairments in static standing balance are highly prevalent among older adults receiving home-based physical therapy.

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Bohannon, Richard W

2012-01-01

Measures of balance are an important component of the physical therapist examination. This study investigated the usefulness of timed static stance durations for identifying balance impairments among patients receiving home-based physical therapy. This study involved the retrospective retrieval of data from the records of 48 patients at least 60 years of age. Their balance was measured under 3 foot configurations; that is, feet apart, feet together, and on each foot. Every patient demonstrated impaired standing balance. Most, but not all could balance 30 seconds with the feet apart or together. Only 19 could maintain balance on each of both feet. Of those who could so balance, none was able to achieve the average time of normal individuals of comparable age. Although not able to identify all aspects of balance, timed durations of stance under different configurations demonstrate a high prevalence of balance impairments among patients receiving home-based physical therapy. As the tests are objective, fast, and require little space, they can be advocated in such a setting.

High immunosuppressive burden in advanced hepatocellular carcinoma patients: Can effector functions be restored?

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Lugade, Amit A; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

2013-07-01

The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

Factors Associated with Quality of Life in Chronic Hepatitis C Patients Who Received Interferon Plus Ribavirin Therapy

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Shu-Chuan Chang

2008-06-01

Conclusion: The study found that patients with chronic hepatitis C who received interferon plus ribavirin therapy had poor quality of life during the treatment period. There was significant difference among patients with different financial stress, and a negative relationship between tangible support and hepatitis quality of life. Financial stress and tangible support are predictors of quality of life for all subjects. The results of this study might assist healthcare personnel to comprehend the quality of life and its related factors in patients with chronic hepatitis C treated with antiviral therapy.

Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

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Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

Relationship between social support and the nutritional status of patients receiving radiation therapy for cancer

International Nuclear Information System (INIS)

Pulliam, L.W.

1985-01-01

The purpose of this descriptive, correlational study was to ascertain if there is a relationship between social support and the nutritional status of patients receiving radiation therapy for cancer. The data collection instruments used included the Norbeck Social Support Questionnaire (NSSQ), the Personal Characteristics Form, the abbreviated Health History, the Flow Sheet for Nutritional Data, and the Interview Schedule. For the analysis of data descriptive statistics were utilized to provide a profile of subjects, and correlational statistics were used to ascertain if there were relationships among the indicators of nutritional status and the social support variables. A convenience sample was comprised of 50 cancer patients deemed curable by radiation therapy. Findings included significant decreases in anthropometric measurements and biochemical tests during therapy. Serial assessments of nutritional status, therefore, are recommended for all cancer patients during therapy in order to plan and implement strategies for meeting the self-care requisites for food and water. No statistically significant relationships were found between the social support variables as measured by the NSSQ and the indicators of nutritional status. This suggests that nurses can assist patients by fostering support from actual and potential nutritional confidants

Late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. III. Disease incidence and life expectancy. [Mice, x radiation

Energy Technology Data Exchange (ETDEWEB)

Peter, C P; Perkins, E H; Peterson, W J; Walburg, H E; Makinodan, T

1975-01-01

The effect of various immunosuppressive treatments on mean life-span and disease incidence have been studied. Significant life shortening was seen only in mice which received X-irradiation early in life and can be ascribed primarily to an increased incidence of certain malignancies. Marginal life shortening was seen in cyclophosphamide-treated animals, however, survival patterns between those and control animals did not differ until 30 months of age and the magnitude of life-shortening never approached that seen in X-irradiated animals. Thymectomy, splenectomy or cortisone treatment did not alter survival. All immunosuppressive treatments enhanced mortality due to non-neoplastic diseases, however, only a small percentage of animals die with these disease entities. With the exception of cortisone all immunosuppressive treatments increased the incidence of neoplastic disease. However, their effects on various neoplastic processes were variable and unpredictable. Four primary patterns in terms of relative immune competence, disease incidence and life expectancy were seen. Thus, immunodepression may or may not correlate with increased disease incidence, which in turn may or may not have a life-shortening effect. These findings are discussed in terms of the marked reduction of both humoral and cell-mediated immunity normally seen in aged mice and the significance of postulated immune surveillance mechanisms to survival.

Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study

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Daniela Cristina Sampaio de Brito

Full Text Available ABSTRACT CONTEXT AND OBJECTIVE : Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. DESIGN AND SETTING : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. METHODS :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. RESULTS : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P < 0.05 and had a marginal trend toward significance with more advanced phases of stress (OR 4.7; CI: 0.99-22.51; P = 0.053. CONCLUSION :Stress and coping strategies may have implications for understanding and managing nonadherent behavior among transplantation patients and should be considered among the strategies for reducing nonadherence.

Efficacy and safety of immunosuppressive therapy in the treatment of seronegative hepatitis associated aplastic anemia

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Chen HF

2014-09-01

Full Text Available Hai-Fei Chen,* Bin-Xian Xu, Hong-Shi Shen,* Zheng-Yang Li, Ling-Juan Jin, Jie-Qing Tang, Jing Wang, Jing-Jing Zhu, Long-Mei Qin, Qing-Ya Cui, Yong-Ya Ren, Tian-Qin Wu Department of hematology, 100th hospital of People’s Liberation Army, Suzhou, Jiangsu province, The People’s Republic of China *These authors have contributed equally to this paper Objective: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA (SNHAA and hepatitis B virus (HBV infection complicating AA (HBVAA, and thereby compare the efficacy of immunosuppressive therapy (IST.Methods: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes.Results: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60% of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00, a quicker response to IST (2.5 months versus 4.5 months, P=0.018, a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03, and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively. No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly

Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis.

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Peng, Xia; Luo, Xin; Hou, Jing-Ying; Wu, Shu-Yun; Li, Liang-Zong; Zheng, Ming-Hua; Wang, Ling-Yun

2017-01-01

Currently, there are no effective therapeutic agents for patients with primary sclerosing cholangitis (PSC). This study aimed to evaluate the safety and efficiency of immunosuppressive agents (IAs) for the treatment of PSC. The literatures were searched using the following keywords singly or in combination: PSC, treatments, IAs. The primary outcome was defined as the need for liver transplantation or mortality. Two hundred sixty six patients from 7 eligible studies were analyzed. IAs had no remarkable effects on the rate of mortality or liver transplantation (relative risk, RR 1.02, 95% CI 0.58-1.62, p = 0.92). Subgroup analyses showed no significant effect of IAs co-administration therapy (IAs co-administered with ursodeoxycholic acid, IA co-administered with IA; RR 1.41, 95% CI 0.40-4.95, p = 0.60). IAs caused adverse events (AEs) such as diarrhea, abdominal pain, and pruritus (RR 1.81, 95% CI 1.07-3.07, p = 0.03). IAs therapy did not significantly improve markers of liver function except for aspartate transaminase (weighted mean difference -9.76, 95% CI -12.92 to -6.6, p IAs administrated as either monotherapy or combination therapy do not reduce the risk of mortality or liver transplantation. IAs monotherapy is associated with AEs. © 2017 S. Karger AG, Basel.

Psychosocial Variables Associated with Immunosuppressive Medication Non-Adherence after Renal Transplantation

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Jennifer Felicia Scheel

2018-02-01

Full Text Available IntroductionNon-adherence to immunosuppressive medication is regarded as an important factor for graft rejection and loss after successful renal transplantation. Yet, results on prevalence and relationship with psychosocial parameters are heterogeneous. The main aim of this study was to investigate the association of immunosuppressive medication non-adherence and psychosocial factors.MethodsIn 330 adult renal transplant recipients (≥12 months posttransplantation, health-related quality of life, depression, anxiety, social support, and subjective medication experiences were assessed, and their associations with patient-reported non-adherence was evaluated.Results33.6% of the patients admitted to be partially non-adherent. Non-adherence was associated with younger age, poorer social support, lower mental, but higher physical health-related quality of life. There was no association with depression and anxiety. However, high proportions of clinically relevant depression and anxiety symptoms were apparent in both adherent and non-adherent patients.ConclusionIn the posttransplant follow-up, kidney recipients with lower perceived social support, lower mental and higher physical health-related quality of life, and younger age can be regarded as a risk group for immunosuppressive medication non-adherence. In follow-up contacts with kidney transplant patients, physicians may pay attention to these factors. Furthermore, psychosocial interventions to optimize immunosuppressive medication adherence can be designed on the basis of this information, especially including subjectively perceived physical health-related quality of life and fostering social support seems to be of importance.

Nocardia brasiliensis Infection Complicating Cryptogenic Organizing Pneumonia.

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Fernandes, Alison M; Sluzevich, Jason C; Mira-Avendano, Isabel

2017-01-01

Pulmonary nocardiosis is a severe and uncommon opportunistic infection caused by Nocardia species. We present a patient with cryptogenic organizing pneumonia who was receiving long-term immunosuppressive therapy, whose treatment course was complicated by cutaneous and pulmonary nocardiosis. Tissue cultures confirmed Nocardia brasiliensis . Nocardiosis should be a diagnostic consideration for patients treated with long-term immunosuppression who have worsening pulmonary symptoms and relapsing pustular skin lesions.

Nocardia brasiliensis Infection Complicating Cryptogenic Organizing Pneumonia

OpenAIRE

Fernandes, Alison M.; Sluzevich, Jason C.; Mira-Avendano, Isabel

2017-01-01

Pulmonary nocardiosis is a severe and uncommon opportunistic infection caused by Nocardia species. We present a patient with cryptogenic organizing pneumonia who was receiving long-term immunosuppressive therapy, whose treatment course was complicated by cutaneous and pulmonary nocardiosis. Tissue cultures confirmed Nocardia brasiliensis. Nocardiosis should be a diagnostic consideration for patients treated with long-term immunosuppression who have worsening pulmonary symptoms and relapsing p...

Predictors of receiving therapy among very low birth weight 2-year olds eligible for Part C early intervention in Wisconsin.

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McManus, Beth Marie; Robert, Stephanie; Albanese, Aggie; Sadek-Badawi, Mona; Palta, Mari

2013-07-11

The Individuals with Disabilities Education Act (Part C) authorizes states to establish systems to provide early intervention services (e.g., therapy) for children at risk, with the incentive of federal financial support. This study examines family and neighborhood characteristics associated with currently utilizing physical, occupational, or speech therapy among very low birthweight (VLBW) 2-year-old children who meet Wisconsin eligibility requirements for early intervention services (EI) due to developmental delay. This cross-sectional analysis used data from the Newborn Lung Project, a regional cohort study of VLBW infants hospitalized in Wisconsin's newborn intensive care units during 2003-2004. We included the 176 children who were age two at follow-up, and met Wisconsin state eligibility requirements for EI based on developmental delay. Exact logistic regression was used to describe child and neighborhood socio-demographic correlates of parent-reported receipt of therapy. Among VLBW children with developmental delay, currently utilizing therapy was higher among children with Medicaid (aOR = 5.3, 95% CI: 1.3, 28.3) and concomitant developmental disability (aOR = 5.2, 95% CI: 2.1, 13.3) and lower for those living in a socially more disadvantaged neighborhood (aOR=0.48, 95% CI: 0.21, 0.98, per tertile). Among a sample of VLBW 2-year olds with developmental delays who are EI-eligible in WI, 4 out of 5 were currently receiving therapy, per parent report. Participation in Medicaid positively influences therapy utilization. Children with developmental difficulties who live in socially disadvantaged neighborhoods are at highest risk for not receiving therapy.

A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study

DEFF Research Database (Denmark)

Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M

2002-01-01

The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up wer...

Risk of fracture in adults on renal replacement therapy

DEFF Research Database (Denmark)

Hansen, Ditte; Olesen, Jonas B; Gislason, Gunnar H

2016-01-01

BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and ex....... Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy....

Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

NARCIS (Netherlands)

van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 1; referees: 2 approved

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Bryony Jenkins

2016-12-01

Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 2; referees: 2 approved

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Bryony Jenkins

2017-02-01

Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of pMHC formation or TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

Genital Tuberculosis as the Cause of Tuboovarian Abscess in an Immunosuppressed Patient

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M. Ilmer

2009-01-01

Full Text Available Background. Although tuberculosis (TB is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB, and in particular female genital tract infection, remains a rare event. Case Report. A 35-year-old human immunodeficiency virus (HIV seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb. Consequently, antituberculotic therapy was provided. Conclusion. In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present.

Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED trial: A multi-centre, double-masked, factorial randomised controlled trial

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Kingston Laura

2008-01-01

Full Text Available Abstract Background Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed. The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. Methods/design Patients with active thyroid eye disease will be randomised to receive (i azathioprine or oral placebo and (ii radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure at 12 months and secondary end-points include quality of life scores and health economic measures. Discussion The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b constructing effective inclusion and exclusion criteria to select for active disease; and (c selecting pragmatic outcome measures. Trial registration Current controlled trials

Clinical Implications for the Timely Diagnosis of Mycobacterium marinum in the Age of Biologic Therapy: A Case Report and Review of the Literature

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Chris J. Lata

2017-01-01

Full Text Available Mycobacterium marinum infections typically present as cutaneous nodular lesions with a sporotrichoid lymphatic spread on extensor surfaces of extremities. The natural history of this infection can be altered if the host is immunosuppressed, leading to disseminated presentations. A detailed exposure history and high degree of suspicion for this indolent pathogen are often required for the correct diagnosis of this disease. We present a case of a 67-year-old male misdiagnosed with seronegative rheumatoid arthritis presenting with rheumatic nodules. Initiation of chronic immunosuppressant therapy including biologic monoclonal antibodies resulted in the exacerbation of initially localized disease to broadly disseminated lymphatic, joint, and myotendinous granulomatous disease and led to delay in the correct diagnosis. Cessation of immunosuppressants, with a prolonged course of antimicrobial therapy and multiple surgical debridements were required for cure.

Retrospective chart review of elderly patients receiving electroconvulsive therapy in a tertiary general hospital

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Mosam Phirke

2015-01-01

Full Text Available Background: Electroconvulsive therapy (ECT is the one of the oldest and effective treatments in psychiatry today. It has been used in a wide variety of psychiatric disorders in both young and old patients. Aims of the study: The present study is a retrospective chart review of geriatric patients receiving ECT as a treatment option in a tertiary care general hospital psychiatry setting. Methodology: The study evaluated ECT records over a 5-year period between the years 2010 and 2014, and it was observed that 23 elderly patients (aged ≥60 years had received ECT. Results: The patients received modified bitemporal ECT using a brief pulse ECT machine and had no major complications. A total of 184 ECT treatments were administered at an average of 8 treatments per case. The major diagnoses of patients were schizophrenia and major depression. The main indications of ECT were intolerance to medication, suicidal behavior and aggression. Out of the 23 elderly patients, 18 (78.26% showed a good response to ECT. The only complication noted was memory loss and confusion in 3 cases. Patients with medical illnesses like hypertension, diabetes and both together received ECT without any complications. Conclusions: This study adds to the scarce database on the use of ECT in elderly patients in India and adds evidence to the fact that ECT is a safe and effective treatment in the elderly.

Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis.

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Yang, Nan; Chen, Jinqiu; Zhang, Hui; Dai, Zhiming; Yao, Huan; Ma, Xiaorong; Bai, Ju; Zhang, Yilin; Zhang, Wanggang

2017-12-01

The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.

Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy.

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Safren, Steven A; Radomsky, Adam S; Otto, Michael W; Salomon, Elizabeth

2002-01-01

The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV.

An analysis of the incidence and related factors for radiation dermatitis in breast cancer patients who receive radiation therapy

International Nuclear Information System (INIS)

Lee, Sun Young; Kwon, Hyoung Cheol; Kim, Jung Soo; Lee, Heui Kwan

2010-01-01

We analyzed the incidence and related factors of radiation dermatitis; at first, to recognize whether a decrease in radiation dermatitis is possible or not in breast cancer patients who received radiation therapy. Of 338 patients, 284 with invasive breast cancer who received breast conservation surgery with radiotherapy at Chonbuk National University Hospital from January 2007 to June 2009 were evaluated. Patients who also underwent bolus, previous contralateral breast irradiation and irradiation on both breasts were excluded. For patients who appeared to have greater than moderate radiation dermatitis, the incidence and relating factors for radiation dermatitis were analyzed retrospectively. A total of 207 and 77 patients appeared to have RTOG grade 0/1 or above RTOG grade 2 radiation dermatitis, respectively. The factors found to be statistically significant for the 77 patients who appeared to have greater than moderate radiation dermatitis include the presence of lymphocele due to the stasis of lymph and lymph edema which affect the healing disturbance of radiation dermatitis (p=0.003, p=0.001). Moreover, an allergic reaction to plaster due to the immune cells of skin and the activation of cytokine and concomitant hormonal therapy were also statistically significant factors (p=0.001, p=0.025). Most of the breast cancer patients who received radiation therapy appeared to have a greater than mild case of radiation dermatitis. Lymphocele, lymphedema, an allergy to plaster and concomitant hormonal therapy which affect radiation dermatitis were found to be significant factors. Consequently, we should eliminate lymphocele prior to radiation treatment for patients who appear to have an allergic reaction to plaster. We should also instruct patients of methods to maintain skin moisture if they appear to have a greater than moderate case of radiation dermatitis.

Energy expenditure in growing preterm infants receiving massage therapy.

Science.gov (United States)

Lahat, Sharon; Mimouni, Francis B; Ashbel, Gina; Dollberg, Shaul

2007-08-01

Massage therapy has been consistently shown to increase weight gain in preterm infants. The mechanism of this presumed improved metabolic efficiency is unknown. We conducted the following trial to test the hypothesis that massage therapy reduces energy expenditure in growing healthy preterm infants. A prospective, randomized, cross-over design study was conducted in 10 healthy, appropriate weights for gestational age, gavage fed preterm infants. Each infant was studied twice: after a period of either 5 days of massage therapy, or after a period of 5 days without massage therapy. Infants were randomized to 5 days of massage followed by 5 days of no massage (n = 5) or the opposite sequence (n = 5). During the massage therapy period, massage was provided daily for three 15 minute periods at the beginning of each 3 hour period every morning. Metabolic measurements were performed by indirect calorimetry, using the Deltatrac II Metabolic cart. Energy expenditure was significantly lower in infants after the 5 day massage therapy period (59.6 +/- 3.6 Kcal/Kg/ 24 hours) than after the period without (63.1 +/- 5.4 Kcal/Kg/ 24 hours) (p = 0.05). Energy expenditure is significantly lowered by 5 days of massage therapy in metabolically and thermally stable preterm infants. This decrease in energy expenditure may be in part responsible for the enhanced growth caused by massage therapy.

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-04-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

International Nuclear Information System (INIS)

Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-01-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Th,e Diagnosis of Atypical Varicella*

African Journals Online (AJOL)

steroid therapy or receiving immunosuppressive drugs run a high risk of the complications of varicella whether they. 'Date received: 7 April 1971. t Present address: Department of Virology, University of Stellenbosch. Medical School, Tiervlei, CP. have contracted a primary infection or are suffering from reactivation of latent ...

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases

International Nuclear Information System (INIS)

Cadman, E.C.; Capizzi, R.L.; Bertino, J.R.

1977-01-01

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p < 0.0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were threated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival

No Evidence for Decay of the Latent Reservoir in HIV-1–Infected Patients Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy

Science.gov (United States)

Gandhi, Rajesh T.; Bosch, Ronald J.; Aga, Evgenia; Albrecht, Mary; Demeter, Lisa M.; Dykes, Carrie; Bastow, Barbara; Para, Michael; Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.; Eron, Joseph J.

2010-01-01

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. PMID:20001856

Care of the patient receiving radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Yasko, J.M.

1982-12-01

External radiation therapy, or teletherapy, is the use of ionizing radiation to destroy cancer cells. Clinical use of ionizing radiation as treatment for cancer began with the discovery of x-rays in 1895, the identification of natural radioactivity (radium) in 1896, and the first reported cure of cancer, a basal cell epithelioma, induced by radiation in 1899. Initially, radiation was administered as a single large dose and produced severe, life-threatening side effects. The basis for the use of ionizing radiation in daily increments for a period of weeks was provided by Regaud in 1922; ten years later, Coutard clinically developed the method of dose fractionation, which remains in use today. Although the use of ionizing radiation as a treatment is over eighty years old, only in recent years have advancements in its clinical application been based on research related to the biologic effect of radiation on human cells. To effectively care for the patient prior to, during, and at the completion of external radiation therapy, the nurse must know the physical and biologic basis of external radiation therapy and its clinical application.

Care of the patient receiving radiation therapy

International Nuclear Information System (INIS)

Yasko, J.M.

1982-01-01

External radiation therapy, or teletherapy, is the use of ionizing radiation to destroy cancer cells. Clinical use of ionizing radiation as treatment for cancer began with the discovery of x-rays in 1895, the identification of natural radioactivity (radium) in 1896, and the first reported cure of cancer, a basal cell epithelioma, induced by radiation in 1899. Initially, radiation was administered as a single large dose and produced severe, life-threatening side effects. The basis for the use of ionizing radiation in daily increments for a period of weeks was provided by Regaud in 1922; ten years later, Coutard clinically developed the method of dose fractionation, which remains in use today. Although the use of ionizing radiation as a treatment is over eighty years old, only in recent years have advancements in its clinical application been based on research related to the biologic effect of radiation on human cells. To effectively care for the patient prior to, during, and at the completion of external radiation therapy, the nurse must know the physical and biologic basis of external radiation therapy and its clinical application

Nocardia brasiliensis Infection Complicating Cryptogenic Organizing Pneumonia

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Alison M. Fernandes

2017-01-01

Full Text Available Pulmonary nocardiosis is a severe and uncommon opportunistic infection caused by Nocardia species. We present a patient with cryptogenic organizing pneumonia who was receiving long-term immunosuppressive therapy, whose treatment course was complicated by cutaneous and pulmonary nocardiosis. Tissue cultures confirmed Nocardia brasiliensis. Nocardiosis should be a diagnostic consideration for patients treated with long-term immunosuppression who have worsening pulmonary symptoms and relapsing pustular skin lesions.

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

Science.gov (United States)

Chauveau, Philippe; Couzi, Lionel; Vendrely, Benoit; de Précigout, Valérie; Combe, Christian; Fouque, Denis; Aparicio, Michel

2009-10-01

The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

Nonadherence to immunosuppression: challenges and solutions

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Moreso F

2015-06-01

Full Text Available Francesc Moreso,1 Irina B Torres,1 Gemma Costa-Requena,2 Daniel Serón1 1Nephrology Department, 2Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, Barcelona, Spain Abstract: Nonadherence to immunosuppressant treatment is common after renal transplantation involving >20% of patients. It is associated with cellular rejection, appearance of donor-specific antibodies, and chronic rejection. It has been estimated that nonadherence can be detected in approximately 50% of failing grafts. Since the evaluation of sociodemographic factors do not allow characterizing the target population, it is necessary to combine different measures of adherence (self-reporting and collateral reporting, pill counts, biological monitoring of blood samples, or others to increase its diagnostic accuracy. During the last decade, it has been shown that the implementation of a multidimensional intervention including information, motivation, and behavioral interventions may lead to an improvement of adherence to treatment. On the other hand, it has been shown that one-off feedback from a nurse, simplification of treatment, or financial assistance programs offered little improvement. Thus, increasing the effectiveness of adherence interventions might have a far greater impact on the long-term outcome of renal transplants than any improvement in specific medical treatments. This will require coordinated action from health professionals, researchers, health planners, and policy makers. Keywords: renal transplantation, nonadherence, immunosuppressive treatment

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

Directory of Open Access Journals (Sweden)

Suenaga M

2015-01-01

Full Text Available Mitsukuni Suenaga, Nobuyuki Mizunuma, Eiji Shinozaki, Satoshi Matsusaka, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev. We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.Methods: Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E, thrombus >40 mm in diameter (S, thrombus involving the superior vena cava (C, and decreased blood flow (V.Results: Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9% by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%. Of these 56 patients, 11 (19.6% received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%, as well as V in two (18.2%, S + V + C in one (9.1%, E + S + V in one (9.1%, E + C in one (9.1%, E in one (9.1%, and C in one (9.1%. All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%. Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%, but there were no treatment

Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

International Nuclear Information System (INIS)

Weigel, S.; Kloska, S.; Freund, M.; Kehl, H.G.

2003-01-01

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

[Predictive factors for failure of non-invasive positive pressure ventilation in immunosuppressed patients with acute respiratory failure].

Science.gov (United States)

Jia, Xiangli; Yan, Ci; Xu, Sicheng; Gu, Xingli; Wan, Qiufeng; Hu, Xinying; Li, Jingwen; Liu, Guangming; Caikai, Shareli; Guo, Zhijin

2018-02-01

To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO 2 ) was significantly decreased, the ratio of oxygenation index (PaO 2 /FiO 2 ) failure of NIPPV. ROC curve analysis showed that the APACHE II score ≥ 20 and PaO 2 /FiO 2 failure of NIPPV, the area under ROC curve (AUC) of the APACHE II score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO 2 /FiO 2 failure of NIPPV in immunocompromised patients.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

Science.gov (United States)

Dizdar, Omer; Tapan, Umit; Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Barista, Ibrahim

2008-05-01

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Predictors of Immunosuppressive Regulatory T Lymphocytes in Healthy Women

International Nuclear Information System (INIS)

Hampras, S. S.; Nesline, M.; Davis, W.; Moysich, K. B.; Wallace, P. K.; Odunsi, K.; Furlani, N.

2012-01-01

Immunosuppressive regulatory T (Treg) cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and Bio Repository (DBBR) program at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood levels of CD4 + CD25 + FOXP3 + Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI), and hormone replacement therapy (HRT) were found to be significant positive predictors of Treg cell levels in peripheral blood (π≤0.05 ). Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (π<0.05) negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.

Immunosuppressive compounds from a deep water marine sponge, Agelas flabelliformis.

Science.gov (United States)

Gunasekera, S P; Cranick, S; Longley, R E

1989-01-01

Two immunosuppressive compounds, 4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol and 4,5-dibromo-2-pyrrolic acid were isolated from a deep water marine sponge, Agelas flabelliformis. Their structures were determined by comparison of their spectral data with those of samples isolated from other organisms. Both compounds were highly active in suppression of the response of murine splenocytes in the two-way mixed lymphocyte reaction (MLR) with little to no demonstrable cytotoxicity at lower doses. In addition, 4,5-dibromo-2-pyrrolic acid suppressed the proliferative response of splenocytes to suboptimal concentrations of the mitogen, concanavalin A (Con A). These results describe for the first time compounds isolated from the marine sponge A. flabelliformis that possess potent in vitro immunosuppressive activity.

Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine.

Science.gov (United States)

Hama, Asahito; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ito, Masafumi; Narita, Atsushi; Kosaka, Yoshiyuki; Tsuchida, Masahiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-11-01

The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony-stimulating factor more frequently and for longer durations than other patients (Paplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia. Copyright© Ferrata Storti Foundation.

EFFICACY OF DIFFERENT IMMUNOSUPPRESSIVE PROTOCOLS WITH CYCLOSPORINE AND METHOTREXATE FOR PATIENTS WITH SYSTEMIC VARIANT OF JUVENILE RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

E.I. Alexeeva

2007-01-01

Full Text Available The article provides information on efficiency of different protocols of therapy with cyclosporine and methotrexate for patients suffering from severe systemic juvenile rheumatoid arthritis (JRA. it shows that a therapy combining cyclosporine with dosage of 4,4 ± 0,58 mg/kg of body per day and methotrexate with dosage of 8,1 ± 1,07 mg/m2 a week is more efficient than monotherapy with each of the same medications of same dosage. Combined use of immunosuppressants induces remission of articular syndrome and constitutional manifestations, as well as provides normalization of laboratory disease activity indications in more than 50% of cases of long clasting systemic variant of JRA on the average a year after the initiation of treatment. Combining cyclosporine with methotrexat improves the curative action of each of the medications without aggravation of their toxic influence. High efficiency of combining cyclosporine with methotrexate makes enables lowering the dosage of glucocorticoids to be taken orally, as well as not prescribing prednisolone to the severe cases of systemic variant of JRA.Key words: juvenile rheumatoid arthritis, treatment, cyclosporine, methotrexate, combined therapy, children.

Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As Augments Dermal Wound Healing in Immunosuppressed Rats.

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Gaurav K Keshri

Full Text Available Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM or low-level laser (light therapy (LLLT emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions. The present study was therefore undertaken to evaluate the photobiomodulatory effects of 810 nm diode laser (40 mW/cm2; 22.6 J/cm2 with pulsed (10 and 100 Hz, 50% duty cycle and continuous wave on full-thickness excision-type dermal wound healing in hydrocortisone-induced immunosuppressed rats. Results clearly delineated that 810 nm PBM at 10 Hz was more effective over continuous and 100 Hz frequency in accelerating wound healing by attenuating the pro-inflammatory markers (NF-kB, TNF-α, augmenting wound contraction (α-SM actin, enhancing cellular proliferation, ECM deposition, neovascularization (HIF-1α, VEGF, re-epithelialization along with up-regulated protein expression of FGFR-1, Fibronectin, HSP-90 and TGF-β2 as compared to the non-irradiated controls. Additionally, 810 nm laser irradiation significantly increased CCO activity and cellular ATP contents. Overall, the findings from this study might broaden the current biological mechanism that could be responsible for photobiomodulatory effect mediated through pulsed NIR 810 nm laser (10 Hz for promoting dermal wound healing in immunosuppressed subjects.

Immunosuppression and risk of cervical cancer

DEFF Research Database (Denmark)

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

2013-01-01

-stage renal disease seem to be at an increased risk of cervical cancer. A higher risk of cervical precancerous lesions was found in patients with some autoimmune diseases; particularly if treated with immunosuppressants. Among behavioral factors weakening the immune system, smoking appeared to strongly...... increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent...

Merkel cell carcinoma in an immunosuppressed patient.

Science.gov (United States)

Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da

2017-01-01

Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

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Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

2014-05-01

Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (Pstatistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including

Rituximab in anti-GBM disease: A retrospective study of 8 patients.

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Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

2015-06-01

Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Site-specific immunosuppression using a new formulation of topical cyclosporine A with polyethylene glycol-8 glyceryl caprylate/caprate.

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Tran, H S; Malli, D; Chrzanowski, F A; Puc, M M; Matthews, M S; Hewitt, C W

1999-05-15

Dermal application of immunosuppressants can be an effective means of achieving site-specific immunosuppression (SITE) on skin allografts in burn wound management and in the treatment of various immune skin disorders. We have previously reported success with topical cyclosporine A (tCsA) in the treatment of skin allograft rejection in rats. Using a new tCsA formulation with a penetration enhancer (PE), polyethylene glycol-8 (PEG-8) glyceryl caprylate/caprate (Labrasol, Gattefossé, St. Priest, France), in a trinary drug delivery system, we hypothesized that we would induce SITE and significantly delay rejection of dual skin allografts in rats. Dual rat skin allografts from Lewis x Brown-Norway (LBN) donors were grafted to Lewis (Lew) recipients. Experimental animals (EXP, n = 7) received a 10-day course of systemic cyclosporine (sCsA, 8 mg/kg/day) followed by topical application. One of the two allografts on each experimental animal received tCsA/PE application (5 mg/kg/day) until sacrifice (tCsA/PE-treated). The other allograft received vehicle only (vehicle-treated). Allogeneic controls (ALLO-CON, n = 9) received no sCsA or tCsA. First signs of rejection were determined based on the initial observation of erythema, hair loss, flakiness, and/or scabs. The mean time to rejection for ALLO-CON allografts was 6.3 +/- 0.7 days (t test, P = 0.0013); for vehicle-treated allografts, 12.3 +/- 3.8 days (paired t test, P = 0.0146); and for tCsA/PE-treated allografts, 25.6 +/- 5.4 days. The disparity of days to rejection between dual allografts in the ALLO-CON group was 0.0 +/- 0.0 day and that between the tCsA/PE- and vehicle-treated dual allografts was 13.3 +/- 3.9 days (t test, P = 0.0016). A new formulation of tCsA in a trinary drug delivery system is successful at delaying the onset of rejection in dual skin allografts in rats by SITE, and PEG-8 glyceryl caprylate/caprate may represent a potentially effective transdermal penetration enhancer. Copyright 1999 Academic

Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice.

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Jindal, Vishal; Arora, Ena; Masab, Muhammad; Gupta, Sorab

2018-05-04

Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. Immunosuppressive tumor microenvironment and dense fibrous stroma are some of the limitation in the success of this novel therapy. However, genetic modifications and combination therapy is the topic of the research to improve its efficacy. In this article, we summarize the current state of knowledge, limitations, and future prospects for CAR T cell therapy in pancreatic cancer.

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3

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Noyes, William R.; Rodriguez, Rey; Knechtle, Stuart J.; Pirsch, John D.; Sollinger, Hans W.; D'Alessandro, Anthony M.; Chappell, Rick; Belzer, Folkert O.; Kinsella, Timothy J.

1996-01-01

Purpose: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. Methods and Materials: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. Results: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months). Conclusion: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant

A Randomized Controlled Trial of Lorazepam to Reduce Liver Motion in Patients Receiving Upper Abdominal Radiation Therapy

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Tsang, Derek S.; Voncken, Francine E.M.; Tse, Regina V. [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Sykes, Jenna [Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto (Canada); Wong, Rebecca K.S.; Dinniwell, Rob E.; Kim, John; Ringash, Jolie; Brierley, James D.; Cummings, Bernard J.; Brade, Anthony [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada); Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca [Princess Margaret Cancer Centre, University Health Network, Department of Radiation Oncology, University of Toronto, Toronto (Canada)

2013-12-01

Purpose: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. Methods and Materials: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. Results: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. Conclusions: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.

Biological Therapy in Systemic Lupus Erythematosus

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Mariana Postal

2012-01-01

Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

Rapid Disease Progression of Liver Metastases following Resection in a Liver-Transplanted Patient with Probable Lynch Syndrome – A Case Report and Review of the Literature

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Noelle Suemi Wassano

2017-03-01

Full Text Available Solid organ transplantation provides life-saving therapy for patients with end-stage organ disease, and its outcomes have been improving dramatically over the past few decades. However, substantial morbidity results from chronic immunosuppressive therapy administered to prevent graft rejection. It predisposes patients to several life-threatening complications, such as opportunistic microbial infections and the development of different types of cancers. Here, we presented the case of a young man with probable Lynch syndrome, who developed an aggressive colon carcinoma after long-term immunosuppressive therapy due to a prior liver transplantation. Based on this case report, we attempt to find an answer to the question about the risk of cancer development or recurrence in patients with familial syndromes receiving long-term immunosuppressive therapy and to find out how it can be minimized. Answering these questions is particularly important, given the facts that disease course is substantially more aggressive among transplanted patients and that prognosis is poor due to lack of immunocompetence, especially in the setting of Lynch syndrome.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

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Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

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Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-06-01

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

Future immunosuppressive agents in solid-organ transplantation.

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Gabardi, Steven; Cerio, Jeffrey

2004-06-01

To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

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Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

2017-01-01

Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation.

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Li, Li; Chaudhuri, Abanti; Chen, Amery; Zhao, Xinmeng; Bezchinsky, Maria; Concepcion, Waldo; Salvatierra, Oscar; Sarwal, Minnie M

2010-12-27

Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients. Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003). There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection. TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

Cerebral involvement in a patient with Goodpasture's disease due to shortened induction therapy: a case report

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Preul Christoph

2009-11-01

Full Text Available Abstract Introduction Goodpasture's disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear. Case presentation A 21-year-old Caucasian man with Goodpasture's disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patient's usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane antibodies were significantly reduced. Previous immunosuppressive therapy was performed without corticosteroids and terminated early after 3 months. The differential diagnostic considerations were cerebral vasculitis and posterior reversible encephalopathy syndrome. Vasculitis could be seen as an extrarenal manifestation of the underlying disease. Posterior reversible encephalopathy syndrome, on the other hand, can be triggered by immunosuppressive therapy and may appear without a hypertensive crisis. Conclusion A combination of central nervous system symptoms with a positive antiglomerular basement membrane test in a patient with Goodpasture's disease should immediately be treated as an acute exacerbation of the disease with likely cross-reactivity of antibodies with the choroid plexus. In our patient, a discontinuous strategy of immunosuppressive therapy may have favored recurrence of Goodpasture's disease.

Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

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Cesarina Giallongo

Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

Significant renoprotective effect of telbivudine during preemptive antiviral therapy in advanced liver cancer patients receiving cisplatin-based chemotherapy: a case-control study.

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Lin, Chih-Lang; Chien, Rong-Nan; Yeh, Charisse; Hsu, Chao-Wei; Chang, Ming-Ling; Chen, Yi-Cheng; Yeh, Chau-Ting

2014-12-01

Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP). From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy. Progressive decrease of aminotransferase levels (p 100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042). Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

International Nuclear Information System (INIS)

Wijkstrom, Martin; Kirchhof, Nicole; Graham, Melanie; Ingulli, Elizabeth; Colvin, Robert B.; Christians, Uwe; Hering, Bernhard J.; Schuurman, Henk-Jan

2005-01-01

Streptozotocin (STZ) is widely applied in animal models of insulin-dependent diabetes mellitus. Adverse effects of STZ mainly concern liver and kidney. In nonhuman primates a single 100-150 mg/kg dose invariably induces diabetes with only rare adverse effects. We report one animal with renal failure necessitating sacrifice. Body weight (age) might be a confounding factor, i.e. older animals might be more vulnerable to STZ-related toxicity. We therefore recommended to administer STZ on a mg/m 2 basis and not on a mg/kg basis. In our islet transplantation program nonhuman primates with STZ-induced diabetes received transplants under chronic immunosuppression including calcineurin inhibitors (cyclosporine, tacrolimus), drugs in the rapamycin class affecting growth factor-induced cell proliferation, and the sphingosine 1-phosphate receptor antagonist FTY720. Four animals developed renal failure and had to be sacrificed, most likely caused by cyclosporine. Kidney histology was typical for cyclosporine toxicity including thrombotic microangiopathy in glomeruli and fibrinoid necrosis of arteries, and for STZ toxicity including acute tubular necrosis and accumulations of erythroid precursors. This adverse effect was observed at a pharmacologically active cyclosporine exposure. Additionally, six diabetic animals without major adverse effects during cyclosporine or tacrolimus treatment are presented. We conclude that cyclosporine facilitates renal dysfunction in animals with STZ-induced diabetes, presumably related to an increased vulnerability to a toxic insult after STZ administration

Feasibility of Using the Helping Alliance Questionnaire II as a Self-Report Measure for Individuals with a Psychiatric Disorder Receiving Music Therapy.

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Hannibal, Niels; Domingo, Maria Rodrigo; Valentin, Jan B; Licht, Rasmus W

2017-11-01

No specific instrument has been developed for measuring alliance during music therapy. To evaluate the feasibility of using the Helping Alliance Questionnaire II (HAq-II) as a self-report measure for individuals receiving treatment for a psychiatric disorder. Specifically, we examined the percent of patients who filled out the questionnaire, and when completed, whether there were any missing items. We also examined internal consistency and associations between patient variables and HAq-II scores. Between October 2013 and April 2014, we invited 45 individuals with a psychiatric disorder, who were also receiving music therapy, to fill out the HAq-II. We also collected clinical data from each person's record. Thirty-one (69%) of the 45 invited patients filled out the HAq-II, and of those completed, only three had missing items. Of the 45 invited patients, thirty (67%) had a diagnosis of schizophrenia or other psychotic disorders, and 11 (24%) were diagnosed with other psychiatric disorders. In terms of diagnosis and other clinical variables, no statistically significant differences were found between the 31 patients who filled out the HAq-II and the 14 patients who did not return the questionnaire. The median HAq-II score was 5.11 (range 3.74-6.00), indicating a relatively high alliance. We did not find any statistically significant associations between the HAq-II scores and potential predictors of interest. The Cronbach's alpha was 0.85. Completion of the HAq-II was fairly high in this group of individuals with psychiatric diagnoses who were receiving music therapy. Internal consistency of the HAq-II was acceptable. Relatively high HAq-II scores suggest a high degree of therapeutic alliance, but the external validity of the HAq-II and the relationship between scores and therapy needs further evaluation. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Palliative medicine consultation for preparedness planning in patients receiving left ventricular assist devices as destination therapy.

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Swetz, Keith M; Freeman, Monica R; AbouEzzeddine, Omar F; Carter, Kari A; Boilson, Barry A; Ottenberg, Abigale L; Park, Soon J; Mueller, Paul S

2011-06-01

To assess the benefit of proactive palliative medicine consultation for delineation of goals of care and quality-of-life preferences before implantation of left ventricular assist devices as destination therapy (DT). We retrospectively reviewed the cases of patients who received DT between January 15, 2009, and January 1, 2010. Of 19 patients identified, 13 (68%) received proactive palliative medicine consultation. Median time of palliative medicine consultation was 1 day before DT implantation (range, 5 days before to 16 days after). Thirteen patients (68%) completed advance directives. The DT implantation team and families reported that preimplantation discussions and goals of care planning made postoperative care more clear and that adverse events were handled more effectively. Currently, palliative medicine involvement in patients receiving DT is viewed as routine by cardiac care specialists. Proactive palliative medicine consultation for patients being considered for or being treated with DT improves advance care planning and thus contributes to better overall care of these patients. Our experience highlights focused advance care planning, thorough exploration of goals of care, and expert symptom management and end-of-life care when appropriate.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Preeti Chhabra

2011-01-01

Full Text Available Clinical islet transplantation is a -cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the -cells regenerative capacity of stem cells.

Current and emerging therapies for the treatment of myasthenia gravis

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Renato Mantegazza

2011-03-01

Full Text Available Renato Mantegazza, Silvia Bonanno, Giorgia Camera, Carlo AntozziDepartment of Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico Carlo Besta, Milan, ItalyAbstract: Myasthenia gravis (MG is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.Keywords: myasthenia gravis, therapy, immunosuppression, thymectomy, plasmapheresis

Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration.

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Rishma Gohil

Full Text Available To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD.This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA. Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient's visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model.The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient's visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively.Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

Survival predictors in paraquat intoxification and role of immunosuppression

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Keng-Hee Koh

2014-01-01

In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4% compared to historical control (30 out of 52 patients (57.7% (p = 0.885 in those with eGFR > 50 ml/min/1.73 m2 or WBC 11,000/μL.

[Uveitis associated with juvenile idiopathic arthritis : Optimization of immunomodulatory therapy].

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Heiligenhaus, A; Tappeiner, C; Walscheid, K; Heinz, C

2016-05-01

Uveitis associated with juvenile idiopathic arthritis (JIA-associated uveitis) is a vision-threatening disorder with a high complication rate. Besides early diagnosis within screening programs an adequate therapy is essential for improvement of the long-term prognosis. Corticosteroid therapy is often insufficient. In addition to conventional immunosuppression, immunomodulatory drugs, so-called biologicals, are novel highly effective treatment modalities. A systematic search of the literature was carried out for biologicals currently used in the treatment of JIA-associated uveitis. Review of current publications, summary of treatment guidelines and discussion of treatment options for therapy refractive patients. In accordance with the current recommendations tumor necrosis factor (TNF) inhibitors are administered if uveitis inactivity cannot be achieved with topical corticosteroids and in the next stage with immunosuppressants (methotrexate preferred). According to the currently available data adalimumab is then preferred. When the effectiveness of TNF inhibitors ceases during long-term administration and/or recurrences, other biological response modifiers are attractive treatment options (e. g. lymphocyte inhibitors or specific receptor antagonists). The TNF inhibitors are of major importance for the treatment of JIA-associated uveitis. Prospective studies and registries would be desirable in order to be able to compare the value of TNF inhibitors and other biologicals and for optimization of treatment recommendations.

Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

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Li, Xiaolin; Wu, Tong; Jiang, Yongjun; Zhang, Zining; Han, Xiaoxu; Geng, Wenqing; Ding, Haibo; Kang, Jing; Wang, Qi; Shang, Hong

2018-05-16

The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunosuppressive Drug Discontinuation in Noninfectious Uveitis From Real-Life Clinical Practice: A Survival Analysis.

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Abásolo, Lydia; Rosales, Zulema; Díaz-Valle, David; Gómez-Gómez, Alejandro; Peña-Blanco, Rayma C; Prieto-García, Ángela; Benítez-Del-Castillo, José Manuel; Pato, Esperanza; García-Feijoo, Julián; Fernández-Gutiérrez, Benjamín; Rodriguez-Rodriguez, Luis

2016-09-01

To assess in uveitis patients the rate of immunosuppressive drug (ISD) discontinuation in real-life clinical practice, comparing this rate among ISDs. Longitudinal retrospective cohort study. We included uveitis patients attending a tertiary eye referral center from Madrid (Spain) between 1989 and 2015, prescribed any ISDs (cyclosporine, methotrexate, azathioprine, anti-TNF drugs, or others). Our main outcome was discontinuation of all ISDs owing to clinical efficacy, inefficacy, adverse drug reaction (ADR), and other medical causes. Discontinuation rates (DRs) per 100 patient-years were estimated. Variables associated with specific-cause discontinuations were analyzed using Cox bivariate and multivariate models. We analyzed 110 patients with 263 treatment courses and 665.2 patient-years of observation. Cyclosporine (66.4%), methotrexate (47.3%), azathioprine (30.9%), and anti-TNFs (30.9%) were the most frequently used ISDs. Treatment was suspended in 136 cases (mostly owing to clinical efficacy [38.2%], inefficacy [26.5%], and ADRs [22.8%]). All-cause DR with 95% confidence interval was 20.4 [17.3-24.2]. Retention rates at 1 and 10 years were 74% and 16%, respectively. In the multivariate analysis, combined treatment exhibited higher DRs owing to clinical efficacy than other ISDs in monotherapy. Conversely, nonbiologic combination therapy with azathioprine exhibited the highest DR owing to ADRs. Clinical efficacy was the most frequent cause for ISD discontinuation, followed by inefficacy and ADRs. DR owing to efficacy was higher for combination therapy. Furthermore, nonbiologic combination therapy with azathioprine was associated with a higher DR owing to ADRs. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

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Stauder, Michael C.; Caudle, Abigail S.; Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A.; Chavez-Macgregor, Mariana; Hunt, Kelly K.; Meric-Bernstam, Funda; Woodward, Wendy A.

2016-01-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

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Stauder, Michael C., E-mail: mstauder@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Caudle, Abigail S. [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chavez-Macgregor, Mariana [Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hunt, Kelly K.; Meric-Bernstam, Funda [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-11-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Intensified pharmaceutical care is improving immunosuppressive medication adherence in kidney transplant recipients during the first post-transplant year: a quasi-experimental study.

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Joost, Robert; Dörje, Frank; Schwitulla, Judith; Eckardt, Kai-Uwe; Hugo, Christian

2014-08-01

Medication adherence is critical for transplant patients because the consequences of non-adherence can result in allograft loss and may be life threatening. A prospective study with 74 renal transplant recipients using a sequential control group design was performed to investigate the impact of a pharmaceutical intensified care programme led by a clinical pharmacist on daily drug adherence during the first year after renal transplantation. Thirty-nine patients of the control group received the already established standardized drug and transplant training, while 35 patients of the intensified care group (ICG) received additional inpatient and outpatient pharmaceutical care and counselling by a dedicated clinical pharmacist. Applied interventions were clustered and classified using the behaviour change technique taxonomy according to Michie. Adherence to immunosuppressive drug therapy was monitored up to 1 year using a medication event monitoring system, pill count (PC), drug holiday (DH) occurrence, Morisky questionnaire and self-report. Sixty-seven patients (35 of the standard care and 32 of the ICG) were analysed. Implementation of DA was significantly (P = 0.014) improved in patients of the ICG (91%) compared with SCG (75%) during the first year after transplantion. Daily adherence measures were already improved within 30-40 days after start of intensified patient care and continued throughout the study period. Intensified care patients also showed significantly better results for taking adherence (P = 0.006), PC (P = 0.008) and DHs (P = 0.001). The additional, intensified pharmaceutical care improved patients' medication adherence remarkably, suggesting that the applied additional care programme has the potential to improve outcomes after organ transplantation. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Prevalence and correlates of cigarette smoking among Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.

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Yan-Min Xu

Full Text Available OBJECTIVE: To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy. METHODS: This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients (male/female: 66.9% vs. 33.1% were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR using data from the 2010 Global Adult Tobacco Survey in China. RESULTS: The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95 ∼ 1.29, 1.07(95%CI = 0.91 ∼ 1.24 and 4.64(95% CI = 2.12 ∼ 8.82, respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking. CONCLUSION: Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness.

The role of basiliximab in the evolving renal transplantation immunosuppression protocol

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Paola Salis

2008-06-01

Full Text Available Paola Salis, Chiara Caccamo, Roberto Verzaro, Salvatore Gruttadauria, Mary ArteroDivision of Nephrology and Division of Abdominal Transplantation, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, ItalyAbstract: Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2 receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR inhibitors for calcineurin inhibitors.Keywords: basiliximab, renal transplantation, IL-2 receptor antagonists, induction, immunosuppression, corticosteroids, calcineurin inhibitors

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

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Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attent...

Understanding alterations in drug handling with aging: a focus on the pharmacokinetics of maintenance immunosuppressants in the elderly.

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Gabardi, Steven; Tullius, Stefan G; Krenzien, Felix

2015-08-01

This review presents current knowledge of the impact of age on the pharmacokinetics of maintenance immunosuppressants. Over the past decade, there has been a steady increase in older patients on organ transplant waiting lists. As a result, the average age of transplant recipients has significantly increased. The survival and quality-of-life benefits of transplantation in the elderly population have been demonstrated. Advancing age is associated with changes in immune responses, as well as changes in drug handling. Immunosenescence is a physiological part of aging and is linked to reduced rejection rates, but also higher rates of diabetes, infections and malignancies. Physiologic changes associated with age can have a significant impact on the pharmacokinetics of the maintenance immunosuppressive agents. Taken together, these age-related changes impact older transplant candidates and may have significant implications for managing immunosuppression in the elderly. Despite the lack of formal efficacy, safety and pharmacokinetic studies of individual immunosuppressants in the elderly transplant population, there are enough data available for practitioners to be able to adequately manage their older patients. A proficient understanding of the factors that impact the pharmacokinetics of the immunosuppressants in the elderly is essential to managing these patients successfully.

The use of irradiated food for immuno-suppressed hospital patients

International Nuclear Information System (INIS)

Pryke, D.C.

1994-01-01

The treatment of leukaemia and other forms of haematological malignancies involves destruction of the bone marrow followed by bone-marrow transplant. This results in patients becoming severely immuno-suppressed. Other diseases result in a similar condition, most notably Acquired Immuno-Deficiency Syndrome (AIDS). Irradiation using radioactive sources or machines has been proposed as a method for preparing foods for immuno-suppressed patients and other high risk groups. Doses of around 30 kGy ensure a total sterility whilst a dose of 10 kGy (the recommended maximum for food available to the general public) results in a significant reduction in the number of pathogenic microorganisms. Irradiation has a number of advantages over other processing methods, in particular that flavour, texture and nutritional changes are limited. This is important as patients are often in a compromised state and need clinical assistance in returning to normal eating habits. In recognition of the potential of irradiated foods for hospital patients this use has been specifically exempted from regulatory control in the UK. This paper reviews the experience in the UK of irradiation-sterilized foods in hospitals. It was found that for practical reasons use is currently restricted. The future prospects for food irradiated at non-sterilized doses are also considered. It is concluded that as well as providing greater choice for consumers (high risk and the general public as a whole) irradiated foods could extend and improved the diets of immuno-suppressed hospital patients; this could be an important factor in recovery. (author)

Severe neuro-Behcet's disease treated with a combination of immunosuppressives and a TNF-inhibitor.

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Korkmaz, Fatma Nur; Ozen, Gulsen; Ünal, Ali Uğur; Kahraman Koytak, Pınar; Tuncer, Nese; Direskeneli, Haner

2016-01-01

Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although

Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During Antituberculosis Therapy: A Case Report.

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Wakamiya, A; Seguchi, O; Shionoiri, A; Kumai, Y; Kuroda, K; Nakajima, S; Yanase, M; Matsuda, S; Wada, K; Matsumoto, Y; Fukushima, S; Fujita, T; Kobayashi, J; Fukushima, N

2018-04-01

Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients. Copyright © 2018 Elsevier Inc. All rights reserved.

Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

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JG Machado

2010-01-01

Full Text Available Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-γ, IL-2, IL-4 and IL-10 by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

Single dose total lymphoid irradiation combined with cyclophosphamide as immunosuppression for human marrow transplantation in aplastic anemia

International Nuclear Information System (INIS)

Kim, T.H.; Kersey, J.H.; Khan, F.M.; Sewchand, W.; Ramsey, N.; Krivit, W.; Coccia, P.; Nesbit, M.E.; Levitt, S.H.

1979-01-01

Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods

Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

DEFF Research Database (Denmark)

Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

2013-01-01

Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

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Nils Schoof

Full Text Available Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs in 43 genes (39 genomic regions related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=0.0004, thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Chhabra, Preeti; Brayman, Kenneth L.

2011-01-01

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells. PMID:22046502

Depressive symptomatology in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

Science.gov (United States)

Lee, Morgan; Jim, Heather S; Fishman, Mayer; Zachariah, Babu; Heysek, Randy; Biagioli, Matthew; Jacobsen, Paul B

2015-04-01

Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls. Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer controls (CA- group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time. Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps depressive symptomatology than both control groups at follow-up (ps depressive symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Oral care of the cancer patient receiving radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Holtzhausen, T [Medical Univ. of Southern Africa, Pretoria (South Africa). Dept. of Community Dentistry

1982-07-01

Radiation therapy is frequently being used for the patient with oral cancer. The survival rate is increasing, due to more effective treatment technique. The question of whether any teeth should be extracted, the mode of therapy and the side effects of radiation like Xerostomia, caries, stomatitis, trismus and osteo-radionecrosis and also post radiation care are discussed.

Factors associated with interest in receiving prison-based methadone maintenance therapy in Malaysia.

Science.gov (United States)

Mukherjee, Trena I; Wickersham, Jeffrey A; Desai, Mayur M; Pillai, Veena; Kamarulzaman, Adeeba; Altice, Frederick L

2016-07-01

Methadone maintenance therapy (MMT) is crucial for HIV prevention and treatment in people who inject opioids. In Malaysia, a large proportion of the prison population is affected by both HIV and opioid use disorders. This study assessed individual preferences and factors associated with interest in receiving MMT among male prisoners meeting criteria for opioid dependence in Malaysia. A convenience sample of 96 HIV-positive and 104 HIV-negative incarcerated men who met pre-incarceration criteria for opioid dependence was interviewed using a structured questionnaire to examine participant characteristics and attitudes toward MMT. Factors associated with interest in prison-based MMT initiation were identified using logistic regression analysis. Among all participants, 85 (42.5%) were interested in receiving MMT within prison. Independent correlates of interest in prison-based MMT were being previously married (AOR=4.15, 95% CI: 1.15, 15.02), previously incarcerated (AOR=5.68, 95% CI: 1.54, 21.02), depression (AOR=3.66, 95% CI: 1.68, 7.98), daily heroin use in the 30days prior to incarceration (AOR=5.53, 95% CI: 1.65, 18.58), and more favorable attitudes toward MMT (AOR=19.82, 95% CI: 6.07, 64.74). Overall, interest in receiving prison-based MMT was low, and was associated with adverse social, mental health, and drug use consequences. Incarceration provides a unique opportunity to initiate MMT for those who need it, however, optimal scale-up efforts must be systemic and address modifiable factors like improving attitudes toward and motivation for MMT. Informed or shared decision-making tools may be useful in improving expectations and acceptability of MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Trichoderma viride infection in a liver transplant recipient

NARCIS (Netherlands)

Jacobs, F.; Byl, B.; Bourgeois, N.; Coremans-Pelseneer, J.; Florquin, S.; Depré, G.; van de Stadt, J.; Adler, M.; Gelin, M.; Thys, J. P.

1992-01-01

A liver transplant recipient developed infection of a perihepatic haematoma due to Trichoderma viride. Before the infection was diagnosed, the patient received intense immuno-suppressive and prolonged antibacterial and anti-fungal therapies. Although the death of the patient was not directly related

Depressive features among adult patients receiving antiretroviral therapy for HIV in Rustenburg district, SA

Directory of Open Access Journals (Sweden)

T Bongongo

2013-06-01

Full Text Available Background. Globally, it is estimated that depressive features occur in 15 - 36% of people suffering from chronic diseases and 60% of people with HIV/AIDS. A high prevalence of mental disorders among HIV-infected individuals has been shown in South Africa and other parts of sub-Saharan Africa. Untreated depression leads to poor adherence to treatment and poor quality of life for patients with chronic diseases. Methods. Using the Zung self-rating scale, we screened for depressive features among adult patients receiving highly active antiretroviral therapy (HAART who attended primary healthcare facilities in the Rustenburg district of North West Province in South Africa during December 2009. Results. Among 117 participants, 81 (69.2 % had mild depressive features, 2 (1.7% had moderate depressive features, 1 (0.9 % had severe depressive features and 33 (28.2% did not have depressive features. Depressive features were more common in males (77.1% than in females (69.5%, and were most common in patients taking the combination of efavirenz, lamivudine and stavudine. Conclusion. Depressive features seem to be common among adult patients receiving HAART and attending primary healthcare facilities in the Rustenburg district.

Polysaccharide from Lentinus edodes inhibits the immunosuppressive function of myeloid-derived suppressor cells.

Directory of Open Access Journals (Sweden)

Hao Wu

Full Text Available 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.

Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

Science.gov (United States)

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

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

Science.gov (United States)

Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

Immunosuppression in irradiated breast cancer patients: In vitro effect of cyclooxygenase inhibitors

International Nuclear Information System (INIS)

Wasserman, J.; Blomgren, H.; Rotstein, S.; Petrini, B.; Hammarstroem, S.

1989-01-01

We have documented in previous studies that local irradiation therapy for breast cancer caused severe lymphopenia with reduction of both T and non-T lymphocytes. Non-T cells were relatively more depressed but recovered within six months. The recovery of T cells, on the other hand, remained incomplete 10-11 years after irradiation. Several lymphocyte functions were also severely impaired. An association was found between prognosis and postirradiation mitogen reactivity of lymphocytes from these patients. Mortality up to eight years after irradiation was significantly higher in patients with low postirradiation phytohemagglutinin and PPD reactivity. The radiation induced decrease in mitogenic response seemed mainly to be caused by immunosuppressive monocytes, which suggests that the underlying mechanism might be mediated by increased production of prostaglandins by monocytes. For this reason we examined the effect of some cyclooxygenase products on different lymphocyte functions and found that prostaglandins A2, D2, and E2 inhibited phytohemagglutinin response in vitro. Natural killer cell activity was also reduced by prostaglandins D2 and E2. The next step was to examine various inhibitors of cyclooxygenase in respect to their capacity to revert irradiation-induced suppression of in vitro mitogen response in lymphocytes from breast cancer patients. It was demonstrated that Diclofenac Na (Voltaren), Meclofenamic acid, Indomethacin, and lysin-mono-acetylsalicylate (Aspisol) could enhance mitogen responses both before and after radiation therapy. This effect was most pronounced at completion of irradiation. On a molar basis, Diclofenac Na was most effective followed by Indomethacin, Meclofenamic acid, and lysin-monoacetylsalicylate

Immunosuppression in irradiated breast cancer patients: In vitro effect of cyclooxygenase inhibitors

Energy Technology Data Exchange (ETDEWEB)

Wasserman, J.; Blomgren, H.; Rotstein, S.; Petrini, B.; Hammarstroem, S.

1989-01-01

We have documented in previous studies that local irradiation therapy for breast cancer caused severe lymphopenia with reduction of both T and non-T lymphocytes. Non-T cells were relatively more depressed but recovered within six months. The recovery of T cells, on the other hand, remained incomplete 10-11 years after irradiation. Several lymphocyte functions were also severely impaired. An association was found between prognosis and postirradiation mitogen reactivity of lymphocytes from these patients. Mortality up to eight years after irradiation was significantly higher in patients with low postirradiation phytohemagglutinin and PPD reactivity. The radiation induced decrease in mitogenic response seemed mainly to be caused by immunosuppressive monocytes, which suggests that the underlying mechanism might be mediated by increased production of prostaglandins by monocytes. For this reason we examined the effect of some cyclooxygenase products on different lymphocyte functions and found that prostaglandins A2, D2, and E2 inhibited phytohemagglutinin response in vitro. Natural killer cell activity was also reduced by prostaglandins D2 and E2. The next step was to examine various inhibitors of cyclooxygenase in respect to their capacity to revert irradiation-induced suppression of in vitro mitogen response in lymphocytes from breast cancer patients. It was demonstrated that Diclofenac Na (Voltaren), Meclofenamic acid, Indomethacin, and lysin-mono-acetylsalicylate (Aspisol) could enhance mitogen responses both before and after radiation therapy. This effect was most pronounced at completion of irradiation. On a molar basis, Diclofenac Na was most effective followed by Indomethacin, Meclofenamic acid, and lysin-monoacetylsalicylate.

Reactivation of cutaneous and mucocutaneous tegumentary leishmaniasis in rheumatoid arthritis patients: an emerging problem?

Directory of Open Access Journals (Sweden)

Regina Maia de Souza

Full Text Available ABSTRACT Rheumatoid arthritis (RA is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX, monoclonal antibodies (mAbs and prednisone. We report an unusual presentation of cutaneous (CL or mucocutaneous leishmaniasis (ML in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

Oral candidiasis in patients receiving radiation therapy for head and neck cancer.

Science.gov (United States)

Deng, Zeyi; Kiyuna, Asanori; Hasegawa, Masahiro; Nakasone, Isamu; Hosokawa, Atsushi; Suzuki, Mikio

2010-08-01

To investigate oral candidiasis in patients with head and neck cancer before, during, and after radiation therapy, and to explore its association with clinical oropharyngeal symptoms. A cohort study. University hospital. Subjects who received radiation therapy (RT) for the treatment of head and neck cancer were divided into two groups: an oral cavity irradiated group (OIRR group, n = 29) and an oral cavity nonirradiated group (ONIRR group, n = 17). A control group consisted of 18 healthy subjects. Patients were examined for signs of oral candidiasis before, during, immediately after, and one month after RT. Mouth and throat soreness (MTS), dysphagia, and xerostomia were evaluated by self-reported questionnaires, and associations between oral candidiasis and these symptoms were analyzed. The incidence of oral candidiasis during RT was significantly higher in the OIRR group (55.2%) than in the ONIRR group (11.8%). Similarly, the occurrence of xerostomia during RT was significantly higher in the OIRR group (86.2%) than in the ONIRR group (52.9%). In the OIRR group, the mean MTS score at the 20th fraction of RT was significantly higher in patients with candidiasis (mean +/- SD, 5.8 +/- 2.1) than in those with RT-induced mucositis without candidiasis (3.7 +/- 2.0). In the OIRR group, 65.2 percent of patients who experienced dysphagia developed oral candidiasis, compared with only 10 percent in the ONIRR group. Oral candidiasis concurrent with oral mucositis due to RT may increase oropharyngeal discomfort during RT. Copyright (c) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

Science.gov (United States)

Paterson, Charlotte; Karatzias, Thanos; Dickson, Adele; Harper, Sean; Dougall, Nadine; Hutton, Paul

2018-04-16

The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and

Estimate of neutron secondary doses received by patients in proton therapy: cases of ophthalmologic treatments

International Nuclear Information System (INIS)

Martinetti, F.

2009-12-01

This research thesis aims at assessing doses due to secondary neutrons and received by the organs of a patient which are located outside of the treatment field. The study focused on ophthalmological treatments performed at the Orsay proton therapy centre. A 75 eV beam line model has first been developed with the MCNPX Monte Carlo code. Several experimental validations of this model have been performed: proton dose distribution in a water phantom, ambient equivalent dose due to secondary neutrons and neutron spectra in the treatment room, and doses deposited by secondary neutrons in an anthropomorphous phantom. Simulations and measurements are in correct agreement. Then, a numeric assessment of secondary doses received by the patient's organs has been performed by using a MIRD-type mathematical phantom. These doses have been computed for several organs: the non-treated eye, the brain, the thyroid, and other parts of the body situated either in the front part of the body (the one directly exposed to neutrons generated in the treatment line) or deeper and further from the treatment field

Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer.

Science.gov (United States)

Scott, Frank I; Mamtani, Ronac; Brensinger, Colleen M; Haynes, Kevin; Chiesa-Fuxench, Zelma C; Zhang, Jie; Chen, Lang; Xie, Fenglong; Yun, Huifeng; Osterman, Mark T; Beukelman, Timothy; Margolis, David J; Curtis, Jeffrey R; Lewis, James D

2016-02-01

Immune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs. To determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti-tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC. In this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012. Exposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery. A second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models. Among 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95

Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis.

Science.gov (United States)

Farahani, Mansour; Mulinder, Holly; Farahani, Alexander; Marlink, Richard

2017-06-01

The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non-AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study's end date was after 2005, all patients were HIV-positive, at least two-thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6-62.3), in developing countries 34.0% (95% confidence interval, 20.3-49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8-23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns.

Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study

OpenAIRE

Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Ant?nio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

2015-01-01

Background Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Methods Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adher...

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

Science.gov (United States)

Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2008-04-01

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.

Hair regrowth in alopecia areata patients following Stem Cell Educator therapy.

Science.gov (United States)

Li, Yanjia; Yan, Baoyong; Wang, Hepeng; Li, Heng; Li, Quanhai; Zhao, Dong; Chen, Yana; Zhang, Ye; Li, Wenxia; Zhang, Jun; Wang, Shanfeng; Shen, Jie; Li, Yunxiang; Guindi, Edward; Zhao, Yong

2015-04-20

Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens. We have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years). Clinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs. Current clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in

The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs

Directory of Open Access Journals (Sweden)

Christine eNeudoerfl

2013-02-01

Full Text Available In the context of kidney transplantation, little is known about the involvement of NK cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e. calcineurin-inhibitors like CyclosporinA vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56dim NK cells was observed with significant differences between CyclosporinA- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR and increased CD94/NKG2A expression in CD56dim NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with PBMC of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and IFN--production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus,NK cells can serve as sensors

Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

LENUS (Irish Health Repository)

Raheem, Omer A

2011-05-28

BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

LENUS (Irish Health Repository)

2012-02-01

BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

Fungal infection knowledge gap in Ethiopia

African Journals Online (AJOL)

EPHA USER33

receiving immunosuppressive therapy, and patients with chronic obstructive lung disease (1). Fungi also play a role in allergic fungal disease such as allergic broncho- pulmonary Aspergilosis (ABPA) and chronic or deep tissue infections. The laboratory diagnosis of fungal infection starts with a simple potassium hydroxide.

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

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Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B; Barbo, Andrea; Lin, Heather Y; Ahmed, Sairah; Chavez-MacGregor, Mariana; Donato-Santana, Christian; Eng, Cathy; Ferrajoli, Alessandra; Fisch, Michael J; McLaughlin, Peter; Simon, George R; Rondon, Gabriela; Shpall, Elizabeth J; Lok, Anna S

2017-09-01

Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients

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

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Fernanda de Oliveira Busarello

2011-12-01

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

Low rate of infectious complications following immunoadsorption therapy without regular substitution of intravenous immunoglobulins.

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Tselmin, Sergey; Julius, Ulrich; Bornstein, Stefan R; Hohenstein, Bernd

2017-11-01

Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis. We conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle. A total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5-16], the median IgG reduction was 82 [11-99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy. Immunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable. Copyright © 2017 Elsevier B.V. All rights reserved.

Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland).

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Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

2016-04-01