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)

The terephthalic acid (TPA) smoke obscurants (M-83 grenade and M-8 smoke pot) were developed by the U.S. Army for training purposes to replace the more toxic hexachloroethane (HC) smoke. Inhalation toxicity testing and chemical characterization of pyrotechnically generated TPA was conducted to assess the health hazard potential of TPA and its combustion products. Fisher 344 rats were subjected to acute and repeated exposures to TPA smoke generated from the M-83 grenade. Acute exposure levels ranged from 150-1,900 mg/m3 for 30 minutes and repeated dose exposures ranged from 128-1,965 mg/m3 for 30 min/day for 5 days. Exposed and control rats were evaluated for toxic signs, and histopathologic changes. During exposure, the rats exhibited slight to moderate lacrimation, rhinorrhea, lethargy and dyspnea, which reversed within 1-hr post-exposure. No deaths occurred, even at the highest smoke concentrations. Histopathological changes were confined to exposure related nasal necrosis and inflammation in both the acute and repeated dose exposures at levels above 900 mg/m3. Chemical characterization of the M-83 grenade and the M-8 smoke pot showed that formaldehyde, benzene and carbon monoxide were the major organic vapor by-products formed. These by-products were above their respective ACGIH threshold limit values at various concentrations, but should not pose a hazard if the smoke is deployed in an open area. Overall, TPA is a safer training smoke to replace the HC smoke.
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PMID:Chemical and toxicological evaluation of pyrotechnically disseminated terephthalic acid smoke. 943 58

Long-term exposure to benzene vapors is associated with hematological diseases such as leukemia, lymphoma and aplastic anemia. CD(1) male mice were randomly assigned to six groups: 1B(10), 1B(15), 1B(20), 2B(10), 2B(15), and 2B(20.) 1B mice were administered 2 ml/kg (1940 mg/kg) subcutaneous injection (in the dorsal region) of benzene 5 days a week, and 2B mice were exposed 3 days a week (Monday, Wednesday and Friday) until a total of 10, 15 and 20 doses were completed. About 48 h after treatment completion, leukocyte, erythrocyte, and bone marrow cells were counted, and spleen histopathology was analyzed. 1B(15) and 1B(20) mice showed lethargy and irritability, 80% body and 42% spleen weight loss (P<0.001), while body and spleen weight loss were less severe in 2B mice (12 and 48%, respectively). After exposure to 20 benzene doses, 1B(20) and 2B(20) mice showed decreased hemoglobin concentrations, and erythrocyte, leukocyte and bone marrow cell counts (37, 34, 80 and 50%, respectively in group 1B(20); P<0.001; and 12, 48, 62 and 62%, respectively in group 2B(20)). Thrombocytopenia occurred only in group 2B. Both benzene-treatment schemes caused aplastic anemia, however, the disease was masked by spleen toxicity in group 1B. Scheme 2 allowed mice survival and caused less non-hematological effects. We establish here a reproducible and inexpensive experimental model to induce aplastic anemia in mice by subcutaneous injection of 2 ml/kg benzene, using two short-term treatment schemes.
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PMID:A model for the induction of aplastic anemia by subcutaneous administration of benzene in mice. 1136 14

One-patient, randomized, double-blind, controlled trials (N-of-1 RCTs) have traditionally been used to assess the efficacy of treatment. At the Drug Safety Clinic, Toronto, this methodology is used to evaluate adverse effects related to medication use, specifically when the symptoms are vague and are in response to more than one medication. Two patients are described with histories of drug allergies to multiple medications; as well, guidelines for conducting N-of-1 trials are summarized. The first patient had a history of prolonged periorbital and generalized weakness lasting up to one week after exposure to a variety of drugs. Because of the ambiguous results of local anesthetic skin testing, an N-of-1 trial was performed using lidocaine without preservative. Two short-lived episodes of blepharospasm and lethargy were observed with placebo; no subjective or objective reaction occurred with active drug. The second patient had a history of prolonged weakness and drowsiness after exposure to many medications; she had been told that she was allergic to all drugs with a benzene ring. During the first N-of-1 trial, generalized weakness was observed with 10 mg of dimenhydrinate and all four placebo doses. During the second N-of-1 challenge using codeine, no unwarranted reactions occurred with either active or placebo drug. Traditional testing of these patients to disprove the clinical symptoms is often difficult because of the anxiety level associated with the patients' past experiences. N-of-1 trials provide a useful alternative for the management of patients with nonspecific symptomatology attributed to drug ingestion.
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PMID:Confirming false adverse reactions to drugs by performing individualized, randomized trials. 1242 52