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 investigational biotherapeutic agent, B43(anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin, has shown substantial anti-leukemic activity in SCID mouse models of human B-lineage leukemia and lymphoma. In this report, we describe the results of a comprehensive preclinical toxicity study which determined the toxicity profile of B43-PAP in BALB/c mice. Administration of unconjugated B43 monoclonal antibody was not associated with any toxicity, whereas B43-PAP caused dose-limiting and cardiac and renal toxicities which were fatal. In addition, B43-PAP also caused multifocal skeletal myofiber necrosis, which was associated with abnormal gait and lethargy. Notably, parenteral administrations of methylprednisolone, pentoxyphylline, or dopamine were able to markedly reduce B43-PAP related toxicity. This study provides a basis for further evaluation of the toxicity of B43-PAP in monkeys and humans.
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PMID:Toxicity profile of the investigational new biotherapeutic agent, B43 (anti-CD19)-pokeweed antiviral protein immunotoxin. 872 29

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.
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PMID:Developmental toxicity study of glycolic acid in rats. 1053 49

Groups of adult male and female rats received exposure to tetrahydrofuran (THF) vapor by inhalation in acute or subchronic exposure scenarios. Acute exposure concentrations were 0, 500, 2500, or 5000 ppm for 6 hr. Evaluations conducted immediately after exposure included clinical observations, motor activity assessments (MA), and a battery of functional tests (FOB) designed to reveal nervous system dysfunction. During exposure to 2500 and 5000 ppm, rats had a diminished or absent startle response to a punctate auditory alerting stimulus. Following exposure to 5000 ppm, male and female rats were lethargic, exhibited abnormal gait or mobility, and splayed rear feet. Lethargy and splayed rear feet were also observed in females exposed to 2500 ppm. During the subsequent FOB, males exposed to 5000 ppm had a lower incidence of palpebral closure, higher incidences of slow or absent righting reflex, and a biphasic pattern of reduced motor activity followed by increased motor activity. Females exposed to 5000 ppm had increased incidences of palpebral closure in the open field, increased incidences of slow or absent righting reflex, and decreased motor activity. During the 14-week subchronic exposure series, daily THF exposure concentrations were 0, 500, 1500, or 3000 ppm, and neurobehavioral evaluations occurred on non-exposure days at approximately monthly intervals. Diminished startle responses to an auditory alerting stimulus were observed during exposure to 1500 or 3000 ppm; however, repeated exposures did not cause additional neurobehavioral or pathological effects. This pattern of effects is suggestive of transient sedation. Despite daily reinstatement of acute sedative effects during repeated exposure with up to 3000 ppm, THF did not produce any persistent or cumulative effects on nervous system structure or function. The demonstrated no-observed-effect level of THF for both acute and subchronic exposure was 500 ppm.
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PMID:Acute and subchronic neurotoxicological evaluation of tetrahydrofuran by inhalation in rats. 1145 95

Medical records of three male and three female callitrichids of four species (Leontopithecus chrysopygus, Leontopithecus rosalia, Callithrix argentata argentata, Callithrix kuhlii) diagnosed with cholelithiasis were reviewed. Ages of affected animals at the time of diagnosis ranged from 2-14 yr. Definitive antemortem diagnosis of cholelithiasis was made in four of the six cases. Chronic weight loss, lethargy, and weakness were seen in all cases. Chronic intermittent diarrhea was seen in three cases. Icterus and abnormal gait were each present in two of the animals. Hematologic and serum biochemical abnormalities included leukocytosis in five cases, elevated bilirubin (direct and indirect) in four cases, and anemia in four cases. Radiographic evidence of choleliths was observed in three cases. Surgical removal of choleliths was successfully performed on two animals. Full necropsies were performed on all cases, and choleliths were believed to contribute to morbidity in all cases. However, inflammatory bowel disease was determined to be the primary cause of weight loss and mortality in at least three animals. All choleliths analyzed were pigment stones, two being primarily composed of cystine.
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PMID:Cholelithiasis in four callitrichid species (Leontopithecus, Callithrix). 1731 11

This report describes the clinical presentation, diagnosis and treatment of a cat with vegetative valvular endocarditis temporally associated with natural infection with Bartonella henselae. Lethargy, abnormal gait and weakness were the main clinical signs that resulted in referral for diagnostic evaluation. Using a novel and sensitive culture approach, B henselae was isolated from the blood. Following antibiotic therapy there was total resolution of clinical signs, the heart murmur, the valvular lesion by echocardiography, and no Bartonella species was isolated or amplified from a post-treatment blood culture. In conjunction with previous case reports, infective endocarditis can be associated with natural B henselae infection in cats; however, early diagnosis and treatment may result in a better prognosis than previously reported.
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PMID:Successful treatment of Bartonella henselae endocarditis in a cat. 2013 59

An adult female Canadian lynx (Lynx canadensis) was presented with a 3-wk history of anorexia and lethargy. Initial examination and diagnostics did not provide a diagnosis. The lynx continued to demonstrate vague clinical signs, including anorexia and an abnormal gait. During follow-up immobilizations 2 wk later, a barium gastrointestinal study revealed a pyloric obstruction. Abdominal exploratory surgery was elected, and a gastrotomy and an enterotomy of the proximal duodenum were performed to remove the pyloric obstruction. The obstruction was determined to be a trichobezoar. Fleas, a likely cause of hair ingestion through grooming, were noted during surgical preparation. The lynx made a full recovery from surgery. Reoccurrence of the trichobezoar was prevented after surgery with the use of monthly flea control and three times a week hairball laxative.
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PMID:Pyloric trichobezoar in a Canadian lynx (Lynx canadensis). 2445 81

Objectives Mirtazapine is commonly used in veterinary medicine at doses of 1.88 or 3.75 mg as an appetite stimulant. The objectives of this study were to determine the most common adverse effects reported and the dose associated with these signs. Methods Records of cats with mirtazapine exposure (2006-2011) were obtained from the American Society for the Prevention of Cruelty to Animals' Animal Poison Control Center. The following parameters were recorded: signalment, weight, outcome, agent ingested, amount ingested, route of exposure, clinical signs observed, intended of use, onset time of signs and duration of signs. Results The 10 most commonly observed adverse effects reported in 84 cats exposed to mirtazapine included vocalization (56.0% of cats; mean dose 2.56 mg/kg), agitation (31.0%; 2.57 mg/kg), vomiting (26.2%; 2.92 mg/kg), abnormal gait/ataxia (16.7%; 2.87 mg/kg), restlessness (14.3%; 3.55 mg/kg), tremors/trembling (14.3%; 2.43 mg/kg), hypersalivation (13.0%; 2.89 mg/kg), tachypnea (11.9%; 3.28 mg/kg), tachycardia (10.7%; 3.04 mg/kg) and lethargy (10.7%; 2.69 mg/kg). Fifty-nine (70.2%) cases were considered accidental ingestions and 25 (29.8%) cases were given mirtazapine as prescribed. The doses associated with signs of toxicity were 15.00 mg (40 cats), 3.75 mg (25 cats), 7.50 mg (four cats), 30.00 mg (one cat), 18.75 mg (one cat), 11.25 mg (one cat), 5.80 mg (one cat) and 1.88 mg (one cat). For cats with available information, the onset of clinical signs ranged from 15 mins to 3 h, and time to resolution of clinical signs ranged from 12-48 h. Conclusions and relevance The greater number of adverse effects at 3.75 mg rather than 1.88 mg suggests that the latter may be a more appropriate starting dose for stimulating appetite while limiting toxicity. The benefit of dispensing exact doses of mirtazapine is implied given the likelihood of accidental administration of a full tablet (15 mg) and the resulting toxicity.
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PMID:Mirtazapine toxicity in cats: retrospective study of 84 cases (2006-2011). 2622 39

A 71-year-old Japanese woman presented with progressive fatigue, lethargy, dysarthria and a gait disorder. Her laboratory data revealed hyponatremia (Na 101 mEq/L), and we started correcting her serum sodium level. Within a few days, she became comatose, bedridden, and was intubated. We diagnosed osmotic demyelination syndrome (ODS) and started performing plasma exchange (PE) on the 39th day of hospitalization. She fully recovered after starting PE, and was discharged on foot unassisted. PE can be a beneficial treatment in patients with chronic ODS.
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PMID:The Improvement of the Outcome of Osmotic Demyelination Syndrome by Plasma Exchange. 2832 Oct 80