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 medical records of 59 dogs with renal amyloidosis were reviewed. Most dogs with amyloidosis were greater than 6 years old, and females were affected more often than males. Beagles, Collies, and Walker Hounds were at increased risk, whereas German Shepherd Dogs and mixed-breed dogs were at decreased risk. Common historical findings were anorexia, polyuria, polydipsia, lethargy, vomiting, and weight loss. Common laboratory findings were leukocytosis, lymphopenia, nonregenerative anemia, hypercholesterolemia, azotemia, hyperphosphatemia, metabolic acidosis, isosthenuria, cylindruria, and proteinuria. Proteinuria was moderate to severe in most dogs, as assessed by qualitative determination of urine protein concentration, urine protein/urine creatinine ratio, and 24-hour urine protein excretion. Conservative medical management was of little value, and survival ranged from 3 to 20 months in 12 dogs for which this information was available. Moderate to severe diffuse global glomerular amyloidosis was detected in all dogs. Medullary amyloid deposition was multifocal and less severe, but was evident in most dogs. Secondary tubulointerstitial and glomerular lesions were mild or absent in most dogs. Thromboembolism was identified in approximately 14% of affected dogs, underlying inflammatory disease in 37%, and neoplasia in 20%. Laboratory indicators of renal function correlated poorly with histologic lesions, with the exception of glomerular amyloid deposition and "chronic renal disease" index with endogenous creatinine clearance.
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PMID:Clinicopathologic findings in dogs with renal amyloidosis: 59 cases (1976-1986). 276 63

Amphethinile is a new spindle poison with a novel structure that has shown activity in the L1210, ADJ/PC6 and Walker carcinoma rodent tumours. In addition the agent appeared to have an improved therapeutic ratio compared to existing spindle poisons and is well absorbed when administered orally. The starting dose for the phase I study was 40 mg m-2 (1/10th mouse LD10) and further patients were studied at 200, 400, 800 and 1200 mg m-2, dose escalation being based on pharmacological monitoring. Significant toxic effects were seen only at 800 and 1200 mg m-2. At these doses patients experienced nausea and vomiting, light headedness during the infusion and varying degrees of lethargy following therapy. Two of six patients at 800 mg m-2 developed severe pain in the tumour bearing area 1-2 h after treatment and one experienced colicky abdominal pain. At 1200 mg m-2 two patients died within 48 h of treatment from what appeared to be vascular causes. Following these episodes the trial was discontinued. Neutropenia and alopecia occurred in two patients, one at 800 and one at 1200 mg m-2. These patients achieved the highest drug exposure in terms of area under the concentration x time curve. It was not possible to achieve an AUC consistently high enough to produce cytotoxic effects due to the occurrence of dose limiting toxicities thus amphethinile cannot at present be recommended for phase II testing by the i.v. route. The dose escalation scheme based on pharmacological monitoring resulted in a considerable saving in the duration of the trial. Further evaluation of this methodology is recommended.
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PMID:A phase I and pharmacokinetic study of amphethinile. 340 47

A 10-year-old Tennessee Walker gelding, with a history of progressive weight loss, intermittent colic and lethargy, had a slight fever, tachycardia, tachypnea, pallor, ascites and marked ventral edema. Blood analyses revealed anemia, leukocytosis, neutrophilia with a left shift, lymphopenia, monocytosis, hypoproteinemia and a slightly increased SDH level. Abdominocentesis produced red-orange fluid with many RBC and an increased fibrinogen content. Rectal palpation revealed a large mass in the left caudal abdominal quadrant. The animal died shortly after resection of the mass. The histopathologic diagnosis was lymphosarcoma, involving the spleen, liver and lung.
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PMID:Splenic lymphosarcoma in a horse. 654 5

Spirogermanium is a new azaspirane antitumor agent, with the metal germanium substituted for a one-carbon moiety in the ring structure. This drug inhibits DNA and RNA synthesis in HeLa cells, is cytotoxic in vitro, and has curative in vivo antitumor activity against the ascitic Walker 256 carcinosarcoma in rats. No hematologic toxicity was recorded during the preclinical toxicologic evaluation. The principal clinical toxic effects observed in this phase I trial were neurologic, manifested as lethargy, dizziness, and ataxia, while a grand mal seizure was produced after an accidental overdose. There was no evidence of hematologic, renal, or hepatic toxicity. A partial response was achieved in a patient with a well-differentiated lymphocytic lymphoma. We recommend that phase II trials be conducted with a twice or thrice weekly dose of 50-80 mg/m2, administered in a 30-minute iv infusion.
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PMID:Phase I clinical trial of spirogermanium. 745 90

The infectivity and pathogenicity of newly discovered baculovirus, CuniNPV (family Baculoviridae, genus Nucleopolyhedrovirus) originally isolated from the mosquito Culex nigripalpus Theobald, was evaluated in laboratory bioassys against thirteen species and four genera of mosquitoes native to the northeastern U.S. Purified virus at a dosage rate of 1.6 x 10(7) occlusion bodies/ml with 10 mM Mg2+ added was used in exposures with second through fourth instars at temperatures ranging from 17 to 27 degrees C. High infection rates and accompanying mortality were achieved in Cx. pipiens L. (83.0-14.4%), Cx. pipiens f. molestus (80.4% infection), and Cx. salinarius Coquillett (48.0-43.1%). Cx. restuans Theobald was also susceptible but infection rates were lower (21.3-12.5%). The gross pathology associated with infection was identical to that reported in Cx. nigripalpus. Infected larvae were lethargic and were often suspended at the water surface. Development of CuniNPV was observed in the nuclei of the midgut epitheial cells in the gastric caeca and posterior region of the stomach of host larvae. One hundred percent mortality was observed in all larvae that exhibited gross symptoms of infection within 4-d p.i. Cx. territans Walker (subgenus Neoculex Dyar) was the only Culex mosquito that was not susceptible. No infections were obtained with any species of Aedes [Ae. vexans (Meigen)], Culiseta [Culiseta morsitans (Theobald)] or Ochlerotatus [Ochlerotatus canadensis (Theobald), Oc. cantator (Coquillett), Oc. communis (De Geer), Oc. excrucians (Walker), Oc. japonicus (Theobald), Ochlerotatus stimulans (Walker), and Ochlerotatus triseriatus (Coquillett)]. The host range of CuniNPV appears to be restricted to Culex mosquitoes within the subgenus Culex. An inhibitory effect on transmission of CuniNPV was observed when a liver powder/Brewer's yeast mixture was used as a source of food reinforcing the critical role of Mg2+ and sensitivity of the infection process to the presence other divalent cations (Cu2+, Fe2+, and Zn2+) in the larval medium that interfered with the infection process. The high infectivity and pathogenicity of CuniNPV for the principal vectors of West Nile virus in North America make CuniNPV an attractive candidate for future development as a biopesticide.
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PMID:Infectivity and pathogenicity of a novel baculovirus, CuniNPV from Culex nigripalpus (Diptera: Culicidae) for thirteen species and four genera of mosquitoes. 1468 Jan 19