Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study analyzes the clinical and bacteriologic features of CSF infections that occurred in patients with neoplastic meningitis treated with thiotepa and methotrexate administered through a subcutaneous reservoir and ventricular catheter (SRVC). Thirty-one patients were treated, and CSF infections occurred in four (13%). Staphylococcus epidermidis was the infecting organism in each case and Pseudomonas maltophilia occurred with S epidermidis in one patient. Fever, headache, lethargy, and evidence of CSF extravasation around the SRVC were the common manifestations of infection. The CSF leukocytosis was the only laboratory abnormality noted. All infections were cured with the appropriate antibiotics and removal of the SRVC. Risk of CSF infection did not seem to be related to the use of high doses of dexamethasone, cranial radiation therapy, or the presence or absence of leukopenia. The SRVCs were replaced and treatment of neoplastic meningitis was resumed in three patients; infection did not recur. A CSF infection during management of neoplastic meningitis may be treated effectively and does not preclude adequate therapy of neoplastic meningitis.
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PMID:CSF infections complicating the management of neoplastic meningitis. Clinical features and results of therapy. 680 96

High doses of adenotk were injected into the cerebrospinal fluid of rats and nonhuman primates (Macaca mulatta). Vector administration was followed by ganciclovir administration for 14 days. Despite the absence of clinical symptoms, analysis of the cerebrospinal fluid (CSF) and histopathological examination of the central nervous system (CNS) of the monkeys (3 weeks after vector injection) were consistent with a viral meningitis. Immunohistochemical analysis of the inflammatory infiltrates in the monkeys revealed the presence of T and B lymphocytes, indicating a combined cellular and humoral immune response to the vector. This latter was supported by the finding of intrathecal anti-adenovirus antibody synthesis. Rats receiving high intrathecal adenotk doses showed a transient and dose-dependent clinical toxicity consisting of lethargy, hyperemic eyes and weight loss. Histopathological examination of the meninges showed a shift from polymorphonuclear infiltrates during the first post-injection days to clusters of mononuclear cells after 7 days. Acute toxicity is probably related to the early, innate immune response to the vector. In a separate experiment, high levels of IL-8 and IL-6, were measured during the first 2-3 post-injection days in the CSF of two monkeys which received intrathecal adenoLacZ. Therefore, these cytokines seem to play an important role in initiating the nonspecific immune response. In one monkey which received adenotk, recombinant adenovirus was cultured from serum samples obtained at the 7th post-injection day. At this time-point, no vector could be isolated from CSF samples. Based on these preclinical data, we recommend careful dose finding for clinical studies that aim to treat patients with leptomeningeal metastases.
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PMID:Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity. 1098 67