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methotrexate and long term effects

Zuzana Sipkova, Elizabeth A Insull, Joel David, Helen E Turner, Shay Keren, Jonathan H Norris
OBJECTIVES: The current first-line treatment for management of active thyroid eye disease (TED) is high-dose intravenous corticosteroids, which have the potential for serious adverse effects. Our aim was to evaluate the effect of steroid-sparing agents (SSAs) in patients with moderate-to-severe active TED, using methotrexate as first-line. METHODS: Presented is a retrospective, four-year, single-centre, consecutive case series of patients with moderate-to-severe TED treated using the Oxford protocol...
August 13, 2018: Clinical Endocrinology
Morouj Ismail, Hiba Hasan, Youmna El-Orfali, Hanan Ismail, Ghada Khawaja
Rheumatoid arthritis (RA) is a painful chronic autoimmune disease affecting the joints. Its first-line therapy, Methotrexate (MTX), although effective in ameliorating the progress of the disease, induces hepatotoxicity over long-term usage. Thus, seeking natural compounds with fewer side effects could be an alternative therapeutic approach. This study aimed to investigate the anti-inflammatory, antiarthritic, and antioxidative effects of synthetic trans -Δ9-tetrahydrocannabinol (Δ9-THC) dissolved in sesame oil (Dronabinol) against MTX in adjuvant-induced arthritis (AIA) rat model...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Ben Othman T, Ghedira H, Ben Abdejlil N, Lakhal A, Torjemane L, Ben Hamed L, Hamida S, Zouari B, Ladeb S
Human recombinant G-CSF reduces the duration of neutropenia following HLA-identical allogeneic bone marrow transplantation. However, its use remains controversial due to the risk of increasing the incidence of acute graft-versus-host disease (aGvHD) and slower platelet recovery. To clarify these risks, we conducted a prospective randomised placebo-controlled trial of filgrastim 5 mcg/kg/day IV from day 7 post-transplant until neutrophil recovery in 145 consecutive adults undergoing HLA-identical allogeneic bone marrow transplantation, with cyclosporine and methotrexate as GvHD prophylaxis...
July 20, 2018: Biology of Blood and Marrow Transplantation
Gustavo A Budmann, Ludmila García Franco, Alejandra Pringe
Purpose: To report a case of pediatric Vogt-Koyanagi-Harada (VKH) successfully treated with infliximab and methotrexate for ten years. Observations: A 9-year-old Hispanic girl with VKH disease, was successfully treated with oral methotrexate 15 mg/week and oral prednisone 40 mg/day (1mg/kg/day). But when oral prednisone was tapered to 10 mg/day over a 3-month period, inflammation recurred. Patient was considered as corticosteroid-dependent thus infliximab 7mg/kg/pulse was started on days 0, 15, 60 and every 60 days thereafter...
September 2018: American Journal of Ophthalmology Case Reports
Jing Wen, Rochelle R Maxwell, Alexander J Wolf, Menachem Spira, Maria E Gulinello, Peter D Cole
Methotrexate is a dihydrofolate reductase inhibitor widely employed in curative treatment for children with acute lymphoblastic leukemia (ALL). However, methotrexate administration is also associated with persistent cognitive deficits among long-term childhood cancer survivors. Animal models of methotrexate-induced cognitive deficits have primarily utilized adult animals. The purpose of present study is to investigate the neurotoxicity of methotrexate in juvenile rats and its relevant mechanisms. The doses and schedule of systemic and intrathecal methotrexate, given from post-natal age 3-7 weeks, were chosen to model the effects of repeated methotrexate dosing on the developing brains of young children with ALL...
September 1, 2018: Neuropharmacology
Luca Quartuccio, Giorgia Gregoraci, Miriam Isola, Salvatore De Vita
AIM: The aim of the present study was to define subsets of patients suffering from polymyalgia rheumatica, where methotrexate (MTX) up to 20 mg/week might be more effective. METHODS: A total of 100 patients with polymyalgia rheumatica treated with MTX were studied. The criteria for MTX introduction were: (i) relapse during the first month of therapy, when tapering glucocorticoids (GC); (ii) requiring long-term GC (i.e. >24 consecutive months); (iii) requiring ≥5 mg/day of prednisone equivalents after 4 months of GC therapy; (iv) GC-related side-effects; and (v) a high risk of GC-related side-effects...
July 6, 2018: Geriatrics & Gerontology International
Edward C Keystone, Ferdinand C Breedveld, Hartmut Kupper, Yihan Li, Stefan Florentinus, Iain Sainsbury
Objective: To evaluate long-term clinical, functional and radiographic outcomes in an open-label extension (OLE) study in patients with rheumatoid arthritis (RA) receiving adalimumab monotherapy or adalimumab+methotrexate following attainment of low disease activity (LDA) with adalimumab+methotrexate. Methods: Methotrexate-naive patients with early RA were randomised to adalimumab, methotrexate or adalimumab +methotrexate in a double-blind, 2-year study. Patients who completed the study and achieved LDA (28-joint Disease Activity Score using C reactive protein (DAS28(CRP)<3...
2018: RMD Open
Shelli Kesler, Robert Ogg, Wilburn Reddick, Nicholoas Phillips, Matthew Scoggins, John Glass, Yin Cheung, Ching-Hon Pui, Leslie Robison, Melissa Hudson, Kevin Krull
Chemotherapeutic agents used to treat acute lymphoblastic leukemia (ALL), the most common cancer affecting young children, have been associated with long-term cognitive impairments that reduce quality of life. Executive dysfunction is one of the most consistently observed deficits and can have substantial and pervasive effects on academic success, occupational achievement, psychosocial function and psychiatric status. We examined the neural mechanisms of executive dysfunction by measuring structural and functional connectomes in 161 long-term survivors of pediatric ALL age 8-21 years who were treated on a single contemporary chemotherapy-only protocol for standard/high or low risk disease...
June 25, 2018: Brain Connectivity
Jinlong Zhao, Xueyan Zhang, Xiangshi Sun, Menghui Zhao, Changhui Yu, Robert J Lee, Fengying Sun, Yulin Zhou, Youxin Li, Lesheng Teng
Methotrexate (MTX), as a disease modifying antirheumatic drug (DMARD), was first line drug to treat rheumatoid arthritis. However, the severe side effect during long term and high dosage usage limit its application. The aim of this study was to develop dual-functional lipid polymeric hybrid pH-responsive nanoparticles to deliver MTX to inflamed joints selectively. The designed MTX loaded stearic acid-octa-arginine and folic acid decorated poly lactic-co-glycolic acid (PLGA) -PK3-based lipid polymeric hybrid nanoparticles (Sta-R8-FA-PPLPNs/MTX) were composed of PK3, Folate-PEG-PLGA, egg PC, and Sta-R8...
September 2018: European Journal of Pharmaceutics and Biopharmaceutics
Diego Strianese
PURPOSE: To present an update on the efficacy and safety of immunosuppressive therapy for thyroid eye disease (TED) and to offer a general recommendation for management of TED, in light of these reports. METHODS: Data were retrieved from a literature search on PubMed, using the following words: thyroid eye disease, immunosuppressant, corticosteroid, methotrexate, azathioprine, cyclosporine, cyclophosphamide, rituximab, etanercept, adalimumab, tocilizumab, teprotumumab, adverse effects, side effects, and complications...
July 2018: Ophthalmic Plastic and Reconstructive Surgery
K Olek-Hrab, J Maj, E Chmielowska, A Jankowska-Konsur, B Olszewska, B Kręcisz, P Iwankowski, M Mackiewicz-Wysocka, Z Adamski, R Nowicki, M Sokolowska-Wojdylo
OBJECTIVE: The first report concerning methotrexate (MTX) in the treatment of Mycosis fungoides (MF) was published in 1964 by Wright. The mechanism of MTX action in the treatment of primary cutaneous T-cell lymphoma (CTCL) has been not explained in detail yet (the anti-inflammatory, immunomodulating, immunosuppressive, and cytostatic actions have been under discussion). PATIENTS AND METHODS: This is a retrospective analysis of 79 MF patients in 4 dermatology clinical centers in Poland...
June 2018: European Review for Medical and Pharmacological Sciences
Ahmed M Fayez, Soad Zakaria, Dina Moustafa
Hepatic injury is a major side effect associated with methotrexate (MTX) therapy resulting from inflammatory reactions and oxidative stress induction. Therefore, liver fibrosis incidence is augmented with long-term MTX therapy. Alpha lipoic acid (ALA) is a naturally occurring compound with potent antioxidant activity. This study explored the hepatoprotective mechanisms of ALA against MTX-induced hepatic injury in rats. Hepatic injury was induced in MTX group by 20 mg/kg body weight ip. injection of MTX. ALA group was pretreated with ALA 60 mmol/kg body weight ip...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Giles W Robinson, Vasilisa A Rudneva, Ivo Buchhalter, Catherine A Billups, Sebastian M Waszak, Kyle S Smith, Daniel C Bowers, Anne Bendel, Paul G Fisher, Sonia Partap, John R Crawford, Tim Hassall, Daniel J Indelicato, Frederick Boop, Paul Klimo, Noah D Sabin, Zoltan Patay, Thomas E Merchant, Clinton F Stewart, Brent A Orr, Jan O Korbel, David T W Jones, Tanvi Sharma, Peter Lichter, Marcel Kool, Andrey Korshunov, Stefan M Pfister, Richard J Gilbertson, Robert P Sanders, Arzu Onar-Thomas, David W Ellison, Amar Gajjar, Paul A Northcott
BACKGROUND: Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure...
June 2018: Lancet Oncology
Marko Barešić, Mirna Reihl, Mario Habek, Nenad Vukojević, Branimir Anić
Behçet's disease is a chronic inflammatory condition of unknown origin characterized by multiple organ involvement. The most common symptoms of Behçet's disease are recurrent oral and/or genital ulcerations in combination with symptoms affecting eyes, skin, central and peripheral nervous system, blood vessels and gastrointestinal tract. We present a 43-year-old female patient with the history of recurrent episodes of genital and oral ulcerations, elevated acute phase reactants and skin lesions. The diagnosis of Behçet's disease has been delayed (for more than 10 years) and reached only after she developed neurological and ocular symptoms...
July 2018: Rheumatology International
Kofi Clarke, Jayakrishna Chintanaboina
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn's disease (CD), ulcerative colitis (UC), and a less common phenotype-indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut...
May 12, 2018: Clinical Reviews in Allergy & Immunology
Sophie E Berends, Anne S Strik, Mark Löwenberg, Geert R D'Haens, Ron A A Mathôt
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use...
May 12, 2018: Clinical Pharmacokinetics
Behzad Heidari, Parnaz Heidari, Karimollah Hajian-Tilaki, Mohammad Ali Bayani, Mansour Babaei
Background: Long-term treatment of rheumatoid arthritis (RA) with prednisolone (PRED) is associated with bone mineral density (BMD) loss. This study aimed to determine the status of BMD in non-compliant women who used PRED alone for RA. Methods: Non-adherent RA taking < 7.5 mg daily PRED without DMARDs for > 6 months, and RA patients taking methotrexate +PRED (RA control) were compared with age-matched non-RA controls. BMD was measured by dual energy x-ray absorptiometry (DXA) method and osteoporosis (OP) was diagnosed by WHO criteria...
2018: Caspian Journal of Internal Medicine
Fengju Rong, Xue Gao, Kexin Liu, Jintao Wu
It has been suggested that endoplasmic reticulum stress (ERS) may induce apoptosis following spinal cord injury (SCI). Methotrexate (MTX) has been used as a long-term therapy regimen for rheumatoid arthritis. However, it is not clear whether MTX remediates SCI by inhibiting ERS. In the present study, to establish an in vitro ERS cell model, PC12 cells were pre-incubated with triglycerides (TG). MTT assays revealed that treatment with 1, 2.5, 5 and 10 µM TG decreased PC12 cell viability in a dose-dependent manner...
May 2018: Experimental and Therapeutic Medicine
Hasib Ahmadzai, Shuying Huang, Chris Steinfort, James Markos, Roger Ka Allen, Denis Wakefield, Margaret Wilsher, Paul S Thomas
Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy...
June 18, 2018: Medical Journal of Australia
H Dickel, T Bruckner, P Altmeyer
BACKGROUND: Fumaric acid esters (FAEs) are an established systemic treatment for moderate-to-severe psoriasis. However, the long-term clinical safety and effectiveness of continuous FAE monotherapy and combination therapy have not been established. OBJECTIVE: To examine the long-term safety and effectiveness of FAEs as monotherapy and in combination with phototherapy or methotrexate in patients with psoriasis treated at a single centre in Germany. METHODS: This monocentric, retrospective observational study, with a follow-up period of up to 32...
April 28, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
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