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)

Three dogs became lethargic and had poor appetites within 2 months after anticonvulsant treatment was initiated to control seizures. Dogs were neutropenic, thrombocytopenic, and anemic and had splenomegaly. Sensitivity to phenobarbital and related anticonvulsants may induce life-threatening leukopenia, thrombocytopenia, and anemia in dogs. Phenobarbital-induced neutropenia in these 3 dogs may have posed a risk for developing bacteremia. It is important for clinicians to be aware of adverse effects so that adequate precautions can be taken. A baseline hemogram should always be obtained before starting anticonvulsant treatment, and periodic hemograms should be obtained to monitor animals. Furthermore, client education should include instructions on recognizing signs of bacteremia, thrombocytopenia, and anemia.
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PMID:Neutropenia and thrombocytopenia in three dogs treated with anticonvulsants. 952 40

Medical records of 3 dogs from North Carolina and 3 dogs from Virginia with ehrlichial morulae in circulating neutrophils were studied retrospectively. Two clinically distinct disease syndromes, including chronic, moderate to severe anemia (n = 3) and polyarthritis (n = 2) were associated with canine granulocytic ehrlichiosis (CGE) in these dogs. One dog was clinically healthy, and abnormalities were not detected during physical examination. Clinical signs were nonspecific and included fever, lethargy, anorexia, vomiting, and diarrhea. The most frequent laboratory abnormalities were normocytic normochromic nonregenerative anemia, moderate thrombocytopenia with large platelets, lymphopenia, and eosinopenia. Considerable variability was found in the serologic responses to Ehrlichia equi, Ehrlichia canis, and Ehrlichia chaffeensis antigens among the 5 dogs for which stored sera were available for indirect fluorescent antibody testing. Polymerase chain reaction amplification and sequencing of portions of the 16S rRNA gene from blood (collected in ethylenediaminetetraacetic acid) of 1 severely anemic dog (dog 3) and 1 polyarthritic dog (dog 4) resulted in DNA sequences nearly identical to the GenBank accessions for Ehrlichia ewingii. The DNA sequence from a 3rd dog (dog 5) was most similar to that of E. canis. Serologic or molecular results support the possibility of E. ewingii, E. equi, and E. canis coinfection or serologic cross-reactivity among canine granulocytic and monocytic Ehrlichia species in dogs from North Carolina and Virginia. Variability in response to tetracycline or doxycycline treatment was noted in these dogs, with more rapid resolution of signs in dogs with polyarthritis. We report the 1st cases of CGE in dogs from North Carolina and Virginia, including recognition of CGE in a healthy dog.
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PMID:Granulocytic ehrlichiosis in dogs from North Carolina and Virginia. 956 Jul 60

Acivicin is a glutamine analogue antimetabolite that inhibits several glutamate-dependent synthetic enzymes. Previous studies of this agent administered on a 72-h continuous i.v. infusion schedule every 3 weeks demonstrated a high rate of severe, albeit reversible, central nervous system (CNS) toxicity at the 30 mg/m2/day dose level. Animal studies have shown that the CNS toxicity of acivicin can be prevented by a concomitant infusion of amino acids postulated to block drug uptake in the CNS by a saturable transport system that is common to endogenous amino acids. This study evaluated the feasibility of escalating acivicin doses in cancer patients by administering acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids (Aminosyn, 10%). Twenty-three patients with advanced malignancies were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks. Reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion, and decreased mental status, occurred in the two patients enrolled at the 60 mg/m2/day dose level, precluding further dose escalation. The maximum tolerated dose (MTD) and recommended dose for additional evaluation of acivicin on this schedule is 50 mg/m2/day. Other toxicities observed were dose-related neutropenia that was grade 4 in four patients (four courses), complicated with fever in three of those patients, and grade 3-4 thrombocytopenia in three patients (three courses). Pharmacokinetics studies performed in 15 patients revealed that the acivicin plasma Css increased from 0.44 microg/ml (range, 0.28-0.59 microg/ml) at the 25 mg/m2/day to 1.06 microg/ml (0.64-1.5 microg/ml) at the 50 mg/m2/dose level. Acivicin Css at the MTD was not significantly higher than previously reported values with single-agent acivicin on the same schedule of administration at the MTD of 25 mg/m2/day dose level (0.60 microg/ml; range, 0.43-0.81 microg/ml). Neurotoxicity did not correlate with acivicin Css, but relationships between exposure to acivicin and the occurrence of both neutropenia and thrombocytopenia were well described by a sigmoidal Emax model. This trial demonstrated that concomitant infusions of amino acid can prevent acivicin-induced CNS toxicity, which allows the dose of acivicin to be escalated 2-fold above previously tolerable doses; however, this effect did not translate in a significant increment in acivicin Css.
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PMID:A Phase I and pharmacological study of the glutamine antagonist acivicin with the amino acid solution aminosyn in patients with advanced solid malignancies. 982 40

Twenty-three episodes of anticoagulant rodenticide toxicity were found in 21 dogs during a retrospective study conducted at The Ohio State University Veterinary Teaching Hospital. Dyspnea (57%), lethargy (48%), coughing/hemoptysis (30%), and pallor (26%) were the most common presenting complaints. Prolonged activated clotting time (ACT), prolonged one-stage prothrombin time (OSPT), and prolonged activated partial thromboplastin time (APTT) were present in all dogs that had not received any prior therapy. Anemia (83%), thrombocytopenia (61%), hypoproteinemia (57%), positive fibrin degradation products (FDPs) (55%, six of 11 tested), and hyperfibrinogenemia (43%, six of 14 tested) were common hematological findings. Treatment included therapy with vitamin K1, blood products, and supportive care. The survival rate was 83%.
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PMID:Anticoagulant rodenticide toxicity in 21 dogs. 993 27

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
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PMID:Isovaleric acidemia with promyelocytic myeloproliferative syndrome. 1019 53

A three-year-old weimaraner was presented with lethargy, anorexia, neck pain and a soft fluctuant swelling in the thoracic inlet. A cough had been noted previously. Clinical examination revealed tachycardia, tachypnoea, pallor and a large subcutaneous swelling, with bruising, suggestive of a haematoma in the thoracic inlet. Thoracic radiographs revealed a cranial mediastinal mass which had the ultrasonographic appearance of fluid, and there was also a marked generalised interstitial lung pattern. Routine haematology revealed severe anaemia and thrombocytopenia, although coagulation tests were within normal limits. A diagnosis of immune-mediated thrombocytopenia was however made on the basis of a positive antiplatelet antibody test and a rapid response to prednisolone therapy. Furthermore, a tentative diagnosis of Angiostrongylus vasorum infection was suggested on the basis of clinical and radiographic findings, although no lungworm larvae were identified on faecal analysis. Despite initiating treatment with fenbendazole, the dog died suddenly. Postmortem examination revealed myocarditis, thrombosing arteritis, pneumonia and chronic membranoproliferative glomerulonephritis associated with A vasorum infection.
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PMID:Immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection in a dog. 1038 68

Following intravenous inoculation with horse blood-infected with the agent of human granulocytic ehrlichiosis (HGE) from a human fatality, two rhesus macaques (Macaca mulatta) exhibited pyrexia and lethargy on days 4-12 postinfection (PI). Hematology revealed neutropenia, thrombocytopenia, and anemia, with ehrlichial morulae in monocytes and neutrophils on days 4-12. Blood was polymerase chain reaction (PCR)-positive on days 4-12 and bone marrow was PCR-positive on day 11. There was a minor increase in gamma-glutamyl transpeptidase on day 12 and serum interferon-gamma levels increased by day 18. Seroconversion occurred on day 20 PI to a titer of 100 by day 22. Western blot bands characteristic of HGE included 25-, 44-, 80-, 94-, 105-, and 125-kD bands. There was generalized lymphohistiocytic infiltration in the liver, spleen, lymph nodes, and other tissues. The liver had focal hepatocyte apoptosis. There was HGE DNA (by PCR) only in the spleen. Comparable findings were not observed in a monkey that received uninfected horse blood as a control. This animal model of human disease is important for further studies of HGE diagnosis, management, and pathogenesis.
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PMID:A simian model of human granulocytic ehrlichiosis. 1040 32

Up to 30% of patients with advanced germ cell tumors will fail induction chemotherapy or will relapse. New agents with activity in this still potentially curable subgroup of patients are needed. Edatrexate (10-ethyl, 10-deaza-aminopterin) is a methotrexate analogue that has preclinical and clinical activity in breast, lung, and head and neck cancers, as well as in non-Hodgkin's lymphomas. A phase II trial of edatrexate in relapsed or refractory malignant germ cell tumors was conducted by the Southwest Oncology Group (SWOG). Twenty-five patients were enrolled in the trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for four weeks followed by a one-week rest period. The treatment course was repeated every five weeks. Among the 23 patients evaluable for response, there were no objective responses with all patients developing progressive disease. Thirteen patients (56%) developed Grade 3-4 toxicities, predominantly stomatitis and malaise/fatigue/lethargy. One patient developed Grade 4 anemia while another developed grade 4 anemia and thrombocytopenia. No patients discontinued treatment due to toxicity nor were there any toxic deaths. Edatrexate administered in this dose and schedule has no antitumor activity and has substantial toxicity in patients with relapsed or refractory germ cell tumors.
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PMID:Phase II trial of edatrexate in relapsed or refractory germ cell tumors: a Southwest Oncology Group study (SWOG 9124). 1042 70

Advanced soft tissue sarcomas (ASTS) refractory to therapy with doxorubicin and/or ifosfamide are highly resistant to therapy with other cytotoxic agents. The efficacy and safety of raltitrexed ('Tomudex') was assessed in patients with ASTS refractory to one or two doxorubicin- and/or ifosfamide-containing regimens in eight centers of the EORTC STBSG group. Raltitrexed was given at 3 mg/m2 as a 15 min i.v. infusion once every 3 weeks. Among the 23 patients [mean age 54 (range 25-73) years] included, 22 patients (15 males and seven females) were eligible and evaluable for response to therapy and 21 were evaluable for toxicity. Patients had previously received chemotherapy in metastatic phase (n=16), as adjuvant treatment (n=5) or both (n=1). The primary tumor was located in the trunk (n=11), in the limbs (n=8) or in the head and neck (n=3). Most patients (n=13) received two courses of raltitrexed (range 1-8). The best response was stable disease in five (23%) patients, while disease progression was noted in 17 patients (77%); the median time to disease progression was 6 weeks. The treatment was well tolerated with only one patient experiencing grade 4 neutropenia and thrombocytopenia, one patient experiencing grade 3 nausea, one lethargy, one headache, and one asthenia. Only one patient experienced febrile neutropenia. Raltitrexed as monotherapy is not an effective treatment for patients with ASTS who failed conventional chemotherapy with doxorubicin and ifosfamide.
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PMID:Phase II study of raltitrexed ('Tomudex') for patients with advanced soft tissue sarcomas refractory to doxorubicin-containing regimens. 1063 Mar 54

The unique clinical and pathological findings in nine Asian (Elephas maximus) and two African (Loxodonta africana) elephants from North American Zoos with a highly fatal disease caused by novel endotheliotropic herpesviruses are described. Identification of the viruses by molecular techniques and some epidemiological aspects of the disease were previously reported. Consensus primer polymerase chain reaction (PCR) combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and the second in African elephants. Disease onset was acute, with lethargy, edema of the head and thoracic limbs, oral ulceration and cyanosis of the tongue followed by death of most animals in 1 to 7 days. Pertinent laboratory findings in two of three clinically evaluated animals included lymphocytopenia and thrombocytopenia. Two affected young Asian elephants recovered after a 3 to 4 wk course of therapy with the anti-herpesvirus drug famciclovir. Necropsy findings in the fatal cases included pericardial effusion and extensive petechial hemorrhages in the heart and throughout the peritoneal cavity, hepatomegaly, cyanosis of the tongue, intestinal hemorrhage, and ulceration. Histologically, there were extensive microhemorrhages and edema throughout the myocardium and mild, subacute myocarditis. Similar hemorrhagic lesions with inflammation were evident in the tongue, liver, and large intestine. Lesions in these target organs were accompanied by amphophilic to basophilic intranuclear viral inclusion bodies in capillary endothelial cells. Transmission electron microscopy of the endothelial inclusion bodies revealed 80 to 92 nm diameter viral capsids consistent with herpesvirus morphology. The short course of the herpesvirus infections, with sudden deaths in all but the two surviving elephants, was ascribed to acute cardiac failure attributed to herpesvirus-induced capillary injury with extensive myocardial hemorrhage and edema.
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PMID:Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesviruses. 1068 40


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