Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mononuclear inflammatory infiltrates are characteristic of experimental allergic encephalomyelitis (EAE). Localized EAE was produced in rats in a single day by passive transfer of living lymphoid cells from immunized donors to non-immunized recipients with thermal brain injuries. When the recipients were pretreated with cyclophosphamide 1 or 2 days before cell transfer, neutrophils in the EAE infiltrates notably increased and mononuclear leukocytes decreased. This neutrophilic form of EAE was produced with cells from donors immunized with whole neural tissue or purified myelin basic protein and with adjuvants of different types. This lesion could not be reproduced if the EAE cells were replaced by EAE serum or by irrelevantly immunized cells, or if their activity was foiled by specific "desensitization" or by use of histoincompatible recipients. The 2-day period during which cyclophosphamide prepared recipients for neutrophilic EAE coincided with a transient lymphopenia and relative neutrocytosis caused by the drug. The passive transfer system made it possible for the drug to unbalance the recipient's hemopoietic system without risking adverse effects on the donor cells. The rapid development of the localized form of EAE made it possible to produce lesions before the recipient's transient imbalance gave way to pancytopenia. The new form of EAE may be useful for investigating autoimmune diseases because the neutrophils which indicate the immunologic injury are instantly recognized as reactive recipient cells. Preexisting conventional (mononuclear) EAE prevented subsequent production of neutrophilic infiltrates. This inhibitory effect may be due to local blockade of vessels by mononuclear cells, a concept for which there is evidence. These considerations suggest that the exudation of neutrophils in the new form of EAE may be due to suppression by cyclophosphamide of the mononuclear component of the inflammatory reaction, with loss of its blockading and protective influence on the vessels.
 ...
PMID:A new form of localized allergic encephalomyelitis featuring polymorphonuclear neutrophilic leukocytes. 555 31

Hoechst Marion Roussel (HMR; now Aventis Pharma) launched leflunomide (HWA-486), an immunomodulator and a disease-modifying antirheumatic drug (DMARD), for the treatment of rheumatoid arthritis (RA) in the US in late 1998 [310118]. By August 2000, the compound had been launched extensively across all of Latin America and in all major European countries [380046]. The compound is also under preclinical investigationfor the prevention of transplant rejection [279727], [304402]. In 1998, HMR filed for approvalfor RA in Europe [279727]. In September 1998, the FDA approved leflunomide for the treatment of active RA in adults and it was launched shortly thereafter [298204], [299258], [310118]. In September 1999, the EU Commission accepted the view of the Committee for Proprietary Medicinal Products, published in May 1999 [326040], [337534], and gave approval for the use of leflunomide in RA in adults [339128]. Lehman Brothers has reported that EU launch was delayed by rare side effects including pancytopenia [354434]. In August 1998, the Arthritis Advisory Committee unanimously recommended that leflunomide be contraindicatedfor pregnancy, and that a pregnancy registry should be established to monitor possible teratogenic effects of the drug [296187]. Kyorin had a licence to develop leflunomide in Japan. Product approval was scheduled for 1998 [159079], but no development has been reported since 1994. Preclinical studies in an animal model of experimental allergic encephalomyelitis (EAE) have shown leflunomide to be a powerful immunosuppressant which may have potential in diseases such as multiple sclerosis [187881]. Leflunomide is rapidly processed in vivo to its active metabolite, A-771726 (RS-61980) [202941], [253615]. In 1996, leflunomide was designated as one of HMR's nine top-priority products, serving an unmet medical need and addressing a potential market in excess of US $500 million per year [221118].
 ...
PMID:Leflunomide Aventis Pharma. 1181 35

In September 2000, a 22-year-old female was admitted to our hospital due to high grade fever, liver enzymes elevation and pancytopenia. Bone marrow aspiration was performed, and hemophagocytosis was present. Epstein-Barr virus (EBV) DNA was positive in her peripheral blood, and we diagnosed the case as EBV-associated hemophagocytic syndrome (EB-VAHS) after excluding other malignancies. The initial therapy including etoposide and dexamethasone was started. As severe leukocytopenia developed, etoposide was stopped and cyclosporin A (CsA) was administered continuously. Four days after administration of CsA, she developed convulsive seizures with loss of consciousness. An MRI demonstrated decreased signal with T1-weighting and high signal with T2-weighting in the subcortical white matter including the posterior lobe. We stopped CsA infusion, and glycerol was administered. Soon the symptom disappeared. When patients developed an episode of convulsive seizure, other diagnostic possibilities were central nervous system (CNS) involvement of hemophagocytosis, EBV encephalitis and acute disseminated encephalomyelitis (ADEM). CsA neurotoxicity must be considered even in the case of EB-VAHS with administration of CsA. As previously reported, Fluid-attenuated Inversion Recovery (FLAIR) imaging improved diagnostic confidence and conspicuity of the T2 hyper intense lesions of CsA neurotoxicity, as well as tacrolimus encephalopathy, typically in the subcortical white matter. Key words; Cyclosporin neurotoxicity; Epstein-Barr virus associated-Hemophagocytic syndrome; Magnetic Resonance Image (MRI).
 ...
PMID:Cyclosporin neurotoxicity with Epstein-Barr virus-associated hemophagocytic syndrome. 1575 52

Alemtuzumab is approved for highly active MS and, in Europe, can be employed after other disease-modifying treatments (DMTs) as an escalation approach or first therapeutic option. The occurrence of secondary autoimmune adverse events and infections differs depending on the employed approach. In the manuscript entitled "Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: report from a single Italian center" by di Ioia M. and collaborators, efficacy and safety data of alemtuzumab were evaluated in a real-world MS population. The aim of the article is to describe in detail the unexpected serious adverse events which occurred in this cohort during and after the administration of the alemtuzumab treatment. Adverse events were observed in 45,7% of the patients. These events were ranked as severe in 23% of the patients. We reported, in particular, cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E and noninfectious meningo-encephalomyelitis.
 ...
PMID:Data of safety in a single-center alemtuzumab treated population. 3218 3