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)

Sixty cats with hematologic abnormalities indicative of non-lymphoid hematopoietic neoplasia were classified into two groups, myelodysplastic syndromes (MDS) and acute myelogenous leukemias (AML), using criteria developed for human patients with similar diseases. Cats with myeloblast counts in bone marrow of less than 30% were classed as MDS and cats with myeloblast counts of 30% or greater were classed as AML. The clinical, laboratory, and postmortem findings in each group were described and compared. Clinical signs of disease were similar in both groups, the most common being inappetance, lethargy, and weakness. Non-regenerative anemia, macrocytosis, neutropenia, and thrombocytopenia were frequent hemogram abnormalities in both groups. Diagnostically useful differences in physical and peripheral blood findings were a higher prevalence of splenomegaly and/or hepatomegaly, thrombocytopenia, and severe anemia in the AML group. Circulating myeloblasts were found only in cats in the AML group. Outcome of disease was similar in both groups; 85% of the cats in each group died or were euthanatized within one week of diagnosis. In cats that were necropsied, extramedullary leukemic infiltrates were found in all cats in the AML group and in none of the cats in the MDS group.
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PMID:Non-lymphoid hematopoietic neoplasia in cats: a retrospective study of 60 cases. 282 80

A 10-year-old girl with a lumbosacral myelomeningocele, managed with clean intermittent catheterization, presented with headache, vomiting, and lethargy. The cerebrospinal fluid (CSF) and urine cultures revealed Escherichia coli, documented to be the same subtype. The organisms were subtyped and the E. coli from both the urine and CSF were noted to be of the same strain. Management consisted of intravenous antibiotics and ultimate replacement of the ventriculoperitoneal shunt. Children with myelodysplasia and CSF shunts should be carefully monitored in a multidisciplinary fashion to anticipate, correctly diagnose, and treat CSF shunt infections associated with bacteriuria.
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PMID:Cerebrospinal fluid shunt infection secondary to Escherichia coli bacteriuria. 804 11

Ilmofosine, an ether lipid derivative of lysophosphatidylcholine has antineoplastic activity in vitro and in vivo. Maximum efficacy in preclinical models is associated with prolonged exposure to the drug. In a Phase I trial of a weekly 2 hour infusion schedule of ilmofosine, a syndrome of lethargy, diminished performance status, and mild hepatotoxicity was dose-limiting at 550 mg/m2. To avoid the higher drug concentrations associated with a brief infusion, a Phase I study of a weekly 24 hour infusional schedule was undertaken in an attempt to maximize dose-intensity. Doses were escalated from 550 to 800 mg/m2. Toxicities included nausea, anorexia, fatigue, and minor elevations of liver function tests. The dose limiting toxicity at 800 mg/m2 was a syndrome of severe abdominal pain. No neutropenia or thrombocytopenia was observed except in one patient who was found to have a myelodysplastic syndrome, thought not to be related to drug therapy. The more prolonged infusion schedule of ilmofosine did not result in a substantial increase in the tolerable dose.
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PMID:Phase I trial of ilmofosine as a 24 hour infusion weekly. 872 47

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 pregnant 2-year-old alpaca was presented for evaluation of progressive weight loss, decreased appetite and lethargy that developed in winter. Haematologic and serum biochemical analyses revealed marked anaemia, leukopenia, severe hypophosphataemia and mild hypocalcaemia. Evaluation of bone marrow core biopsies and aspirates revealed an increased proportion of immature haematopoietic cells, without sufficient numbers of blast cells to be termed an acute myeloid leukaemia (AML). 1 The haematological and bone marrow findings were suggestive of myelodysplastic syndrome (MDS). The anaemia, leukopenia, lethargy and weight loss remained refractory to medical therapy and the alpaca was euthanased on humane grounds.
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PMID:Myelodysplasia, hypophosphataemia, vitamin D and iron deficiency in an alpaca. 1143 96

PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this Phase I study was to evaluate the safety, tolerability, biologic activity and pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous dosing schedule in patients with primary refractory or relapsed acute myeloid leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK monotherapy was ineffective could receive PTK/ZK combined with standard induction chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated according to standard bone marrow and peripheral blood criteria. At 1000 mg b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and anorexia were observed. Other adverse events related to PTK/ZK were dizziness, weakness, fatigue, diarrhea and pruritus; these were generally mild and reversible. Pharmacokinetic data showed that steady state was reached by day 14, there was no accumulation with repeat dosing and there was no significant increase in exposure at steady state beyond the maximum tolerated dose (MTD). Complete remission was observed in five of 17 AML patients treated with PTK/ZK combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally b.i.d. The drug is generally well tolerated and can be given in combination with chemotherapy for patients with MDS and AML.
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PMID:Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. 1661 23

A 4-year-old, spayed female, domestic shorthair cat was presented for lethargy, nonregenerative anemia, and inappetence. Results of a CBC included macrocytic, normochromic, nonregenerative anemia and a glucocorticoid-associated leukogram. On blood smear examination, neutrophils had abnormal features including hyposegmentation and a diffuse chromatin pattern with nuclear filament formation and nuclear blebbing. Microscopic examination of a roll preparation of bone marrow revealed hypolobulated megakaryocytes with asynchronous maturation of nuclei. The granulocytic to erythrocyte (G:E) ratio was 76. Segmented neutrophils had asynchronous maturation and dysplastic features. The entire erythroid lineage was markedly decreased for the degree of anemia and rare dysplastic features were noted in erythroid precursor cells. The interpretation of bone marrow findings was erythroid hypoplasia, megakaryocytic dysplasia, and granulocytic hyperplasia with dysplasia. Histopathologic examination of a bone marrow core sample also revealed myeloid hyperplasia and erythroid hypoplasia. The result of a direct immunofluorescence assay for FeLV performed on the bone marrow roll preparation was positive. A diagnosis of dysmyelopoiesis associated with FeLV infection was made. This case was unique in that the dysplastic changes occurred in cell lines that did not have associated cytopenias. The dysmyelopoiesis most closely resembled myelodysplastic syndrome with refractory cytopenia (MDS-RC); however, secondary dysmyelopoiesis could not be ruled out.
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PMID:Blood smear from a cat: features to "dys"cover. 1712 56

An 18-year-old female alpaca was presented to the Colorado State University Veterinary Teaching Hospital for chronic ill thrift over a 1-year period. Six weeks previously, an infected left mandibular cheek tooth was removed by oral extraction. On physical examination the patient was cachectic, lethargic, and weak. Abnormalities on the CBC included neutropenia, thrombocytosis, and severe nonregenerative, macrocytic, hypochromic anemia. Dysplastic nucleated erythrocytes and micromegakaryocytes were observed on the peripheral blood smear. Neutrophils, bands, and metamyelocytes appeared markedly toxic. Numerous blasts containing variable numbers of fine azurophilic granules were also observed. Based on their morphology, the cells were interpreted to be progranulocytes and myeloblasts, and a presumptive diagnosis of acute myeloid leukemia (AML) was made. The blast cells accounted for 60% of the nucleated cell population on bone marrow aspirates, further supporting a diagnosis of AML with multilineage dysplasia. Post mortem examination showed infiltration of the neoplastic cells into spleen, liver, kidney, and lymph nodes. Based on histologic findings, the morphologic diagnoses were disseminated myeloid neoplasia, chronic regionally extensive tooth root abscess, and membranous glomerulonephritis. The neoplastic cells were CD172a-positive on flow cytometry, chloroacetate esterase-positive by cytochemistry, and myeloperoxidase-positive by immunohistochemistry, confirming myeloid origin. To our knowledge, this is the first case of AML with multilineage dysplasia in an alpaca, with only one other case of myelodysplasia described previously in this species.
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PMID:Acute myeloid leukemia with multilineage dysplasia in an alpaca. 1876 21

We reported 37 patients with myelodysplastic syndromes (MDS) of refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts who were treated with cyclosporin A (CyA)/thalidomide combination therapy. Of them, 19 patients (19/37, 51.4%) achieved a hematologic improvement and erythroid response (HI-E); 9 patients (9/29, 31.0%) achieved hematologic improvement and platelet response (HI-P) and 7 patients (7/33, 21.2%) achieved hematologic improvement and neutrophil response (HI-N). 15 of 32 (46.9%) transfusion-dependent patients achieved independence from transfusion. The median response duration of HI-E, HI-P and HI-N were 88 (4-108) weeks, 78 (8-84+) weeks and 78 (10-84+) weeks, respectively. Some patients presented with I or II grade hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rash or sense of numbness. Therefore, CyA combined with thalidomide appears to be useful and is relatively well-tolerated for patients with MDS.
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PMID:Cyclosporin A and thalidomide in patients with myelodysplastic syndromes: Results of a pilot study. 2059 81

A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets. Bone marrow examination revealed marked myeloid and megakaryocytic hyperplasia with 7% blasts, erythroid hypoplasia, and trilineage dysplasia. Flow cytometric analysis confirmed that bone marrow cells were mostly of neutrophil lineage, with reduced expression of common leukocyte antigens (CD45, CD18) and neutrophil-specific antigen. Bone marrow cells were cytogenetically analyzed for the breakpoint cluster region-Abelson oncogene using multicolor fluorescent in situ hybridization. The genetic aberration was present in 7% of cells, which was a negative result (>10% of cells is considered positive). Euthanasia was elected. Histologic examination showed extensive infiltration of multiple organs by neoplastic myeloid cells, with effacement of lymph node and splenic architecture. The final diagnosis was atypical chronic myeloid leukemia (aCML), an uncommon myeloproliferative disorder with features of myelodysplastic syndromes (dysplasia) and chronic leukemia (neutrophilic leukocytosis with <20% marrow blasts, extramedullary infiltrates). The trilineage dysplasia, lack of monocytosis, and supporting cytogenetics distinguish aCML from CML, chronic neutrophilic leukemia, and chronic myelomonocytic leukemia.
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PMID:Atypical chronic myeloid leukemia in a German Shepherd Dog. 2820 62


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