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)

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.
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PMID:Interferon in essential thrombocythaemia. 193 8

Basophilic leukemia with thrombocytosis was diagnosed in a 4-year-old Shih Tzu. This diagnosis was based on cytochemical staining and cytologic examination of blood and bone marrow smears. Hydroxyurea, an inhibitor of DNA synthesis, at a dose of 50 mg/kg PO bid induced hematologic remission after 7 days of treatment. Adverse effects observed included pruritus, erythema of the ventral abdomen, generalized alopecia, and possibly, diabetes mellitus. The dog remained in remission for 21 months before becoming lethargic, at which time the owners requested euthanasia but did not allow a necropsy.
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PMID:Basophilic leukemia in a dog. 912 96

Primidone is used alone or with other anticonvulsants in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy. Primidone was nominated by the National Cancer Institute for 2-year toxicology and carcinogenicity studies due to its human use as an anticonvulsant. Male and female F344/N rats and B6C3F1 mice received primidone (greater than 99% pure) in feed for 14 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 14-DAY STUDY IN RATS: Five male and five female rats were exposed to 0, 1,250, 2,500, 5,000, 10,000 or 20,000 ppm primidone (equivalent to average daily doses of approximately 120, 240, 500, 970, or 1,100 mg primidone/kg body weight to males and 120, 240, 500, or 900 mg/kg to females) in feed for 14 days. All 20,000 ppm females died before the end of the study as did one 10,000 ppm male and two 20,000 ppm males. The mean body weights of 10,000 ppm males and females and 20,000 ppm males were significantly less than those of the controls. Feed consumption by all exposed rats was generally similar to that by the controls. Males and females in the 10,000 and 20,000 ppm groups were observed to have eye discharge, ataxia, and abnormal posture and were thin and lethargic. 14-DAY STUDY IN MICE: Five male and five female mice were exposed to 0, 625, 1,250, 2,500, 5,000 or 10,000 ppm primidone (equivalent to average daily doses of approximately 100, 200, 400, or 800 mg/kg body weight to males and 100, 250, 500, or 900 mg/kg to females) in feed for 14 days. All mice in the 10,000 ppm groups and one male and one female mouse in the 5,000 ppm groups died on day 3 of the study. The mean body weights of mice in the 625, 1,250, 2,500, and 5,000 ppm groups were similar to those of the controls. Feed consumption by all exposed mice was generally similar to that by the controls. Males and females in the 10,000 ppm groups were observed to have abnormal posture, ataxia, and lethargy. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 0, 300, 600, 1,300, 2,500, or 5,000 ppm primidone (equivalent to average daily doses of approximately 20, 40, 100, 200, or 400 mg/kg) in feed for 14 weeks. All rats survived to the end of the study. The mean body weights of male and female rats in the 2,500 and 5,000 ppm groups were significantly less than those of the controls. Feed consumption by all exposed rats was generally similar to that by the controls. A minimal to mild exposure-related thrombocytosis occurred on day 22 and at week 14 in all exposed groups of male rats and in females in the 1,300 ppm or greater groups. A minimal decrease in hemoglobin concentration occurred in 2,500 and 5,000 ppm male and female rats on day 22 and at week 14. The incidences of centrilobular hepatocyte hypertrophy in male rats exposed to 600 ppm or greater and in female rats exposed to 1,300 ppm or greater were significantly greater than those in the controls. The severity of chronic nephropathy in male rats exposed to 1,300 ppm or greater increased with increasing exposure concentration. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 0, 300, 600, 1,300, 2,500, or 5,000 ppm primidone (equivalent to average daily doses of approximately 50, 100, 200, 400, or 1,000 mg/kg to males and 60, 120, 220, 440, or 1,100 mg/kg to females) in feed for 14 weeks. Three male and two female mice in the 5,000 ppm group died during week 1 of the study. The final mean body weights of all exposed groups were similar to those of the controls. Feed consumption by male mice in the 5,000 ppm group was slightly greater than that by the controls; this may have been due to feed spillage. Male and female mice in the 5,000 ppm groups were ataxic and lethargic. Compared to controls, the estrous cycle lengths of females exposed to 1,300, 2,500, or 5,000 ppm were significantly longer. The liver weights of male and female mice exposed to 600 po 600 ppm or greater were significantly greater than those of the controls. The incidences of centrilobular hepatocyte hypertrophy in all exposed males and in females exposed to 600 ppm or greater and the incidences of cytoplasmic alteration of the adrenal gland and hematopoietic cell proliferation of the spleen in 2,500 and 5,000 ppm males and in 5,000 ppm females were significantly greater than in the controls. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 0, 600, 1,300, or 2,500 ppm primidone (equivalent to average daily doses of approximately 25, 50, or 100 mg/kg) in feed for 2 years. Survival, Body Weights, and Feed Consumption Survival of the 1,300 and 2,500 ppm males was sig nificantly less than that of the controls. The mean body weights of males and females in the 2,500 ppm groups were less than those of the controls, beginning at week 29 for males and week 17 for females; the mean body weights of 1,300 ppm males and females were less than those of the controls during the second year of the study. Feed consumption by all exposed groups of rats was generally similar to that by the controls. Pathology Findings Male rats exposed to primidone had increased inci dences of thyroid gland follicular cell neoplasms (adenoma and/or carcinoma). All exposed groups of male rats had follicular cell adenomas or carcinomas (combined) at incidences above the historical control range, with the highest incidence in the 1,300 ppm group. Hepatocyte cytoplasmic vacuolation and centrilobular hypertrophy were associated with primidone exposure in male and female rats. These changes were more severe in females than in males and the incidences in all exposed groups of females were significantly greater than those in the controls. Females in the 2,500 ppm group had an increased incidence of hepatocellular eosinophilic foci. In 2,500 ppm males, the incidence of renal tubule hyperplasia was greater than that in the controls in the standard evaluation. Additional hyperplasias were found in the extended evaluation, and the incidences in exposed groups of males were significantly greater than that in the controls. In the extended evaluation, the incidence of renal tubule adenoma in 2,500 ppm males was significantly increased. The incidence of adenoma or carcinoma (combined) in 2,500 ppm males in the combined standard and extended evaluations were marginally increased over those in the controls. Male rats had an exposure-related increase in the severity of chronic nephropathy, which probably accounted for the reduced survival in the 1,300 and 2,500 ppm groups. The incidences of kidney cysts were increased in 1,300 and 2,500 ppm males. Hyperparathyroidism, secondary to the loss of renal function, was present in many exposed male rats. The incidences of parathyroid gland hyperplasia in all groups of exposed males were significantly greater than that in the controls. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to dietary levels of 0, 300, 600, or 1,300 ppm primidone (equivalent to average daily doses of approximately 30, 65, or 150 mg/kg to males and 25, 50, or 100 mg/kg to females) in feed for 2 years. Survival, Body Weights, Feed Consumption, and Clinical Findings Survival of the 1,300 ppm males was significantly less than that of the controls. During the second year of the study, the mean body weights of 1,300 ppm male and female mice were less than those of the controls. The final mean body weights of 600 ppm males and females were less than those of the controls. Feed consumption by all exposed groups of mice was similar to that by the controls. During the latter part of the study, a treatment-related increase in the number of animals with swelling of the abdominal area was observed; necropsy revealed that the swelling was due to liver nodules/masses. Pathology Findings The liver was a target organ in both male and female mice. The incidences and multiplicities of hepatocellular neoplasms (hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma) in all exposed groups of males and females (except hepatoblastoma in females) were significantly greater than those in the controls. The incidences of hepatocellular adenoma or carcinoma (combined) and hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma (combined) in all exposed groups exceeded the historical control ranges in 2-year NTP studies. The incidences of centrilobular hepatocyte hypertrophy were increased in exposed groups of males and females, and the severities increased with increasing exposure concentration. The incidences of cytoplasmic vacuolization were increased in all exposed groups of females and in 300 ppm males. Incidences of eosinophilic focus in all exposed groups of females were significantly greater than those in the controls. Proliferative changes occurred in the thyroid gland in an exposure-related manner in male and female mice. Incidences of follicular cell hyperplasia were increased in all exposed groups of males and in 600 and 1,300 ppm females, but incidences of follicular cell adenomas were increased only in male mice. GENETIC TOXICOLOGY: Primidone was mutagenic in Salmonella typhimurium strain TA1535 in the absence of S9 activation only; no mutagenicity was detected in strain TA98, TA100, or TA1537, with or without S9. Primidone did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. The single in vivo study with primidone, a mouse bone marrow micronucleus test, also gave negative results. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was equivocal evidence of carcinogenic activity of primidone in male F344/N rats based on a marginal increase in thyroid gland follicular cell neoplasms, primarily adenomas, and a marginal increase in renal tubule neoplasms. There was no evidence of carcinogenic activity of primidone in female F344/N rats exposed to 600, 1,300, or 2,500 ppm. There was clear evidence of carcinogenic activity of primidone in male B6C3F1 mice based on the increased incidences of hepatocellular neoplasms, and the increased incidence of thyroid gland follicular cell adenomas was also considered to be chemical related. There was clear evidence of carcinogenic activity of primidone in female B6C3F1 mice based on the increased incidences of hepatocellular neoplasms. Exposure of rats to primidone resulted in increased incidences of hepatocyte cytoplasmic vacuolization and centrilobular hypertrophy in males and females and eosinophilic foci in females. The increased severity of nephropathy and increased incidence of renal tubule hyperplasia in male rats were related to primidone exposure. Exposure of male mice to primidone resulted in hepatocyte centrilobular hypertrophy and thyroid gland follicular cell hyperplasia. Exposure of female mice to primidone resulted in hepatocyte centrilobular hypertrophy and cytoplasmic vacuolization, eosinophilic focus, and thyroid gland follicular cell hyperplasia. Synonyms: 5-Aethyl-5-phenyl-hexahydropyrimidin-4,6-dion; 2-deoxyphenobarbital; 2-desoxyphenobarbital; desoxyphenobarbitone; 5-ethyldihydro-5-phenyl-4,6 (1H,5H)-pyrimidinedione; 5-ethylhexahydro-4,6-dioxo-5-phenylphrimidine; 5-ethylhexahydro-5-phenylpyrimidine-4,6-dione; 5-ethyl-5-phenylhexahydropyrimidine-4,6-dione Trade names: Cyral; Hexadiona; Hexamidine; Lepimidin; Lepsiral; Majsolin; Midone; Milepsin; Misodine; Misolyne; Mizodin; Mizolin; Mylepsin; Mylepsinum; Mysedon; Mysoline; Prilepsin; Primacione; Primaclone; Primacone; Primakton; Primadon; Prysoline; Pyrimidone; ROE 101; Sertan
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PMID:NTP Toxicology and Carcinogenesis Studies of Primidone (CAS No. 125-33-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). 1257 87

A 7-year-old male German Shepherd dog with a history of lethargy, weight loss and severe anemia was referred to the University of Florida Veterinary Medical Teaching Hospital for examination. Abnormal laboratory findings included a normocytic and normochromic anemia, thrombocytosis, eosinophilia, basophilia and hyperproteinemia. An increased pulmonary density in the caudal lung lobes was observed on thoracic radiographs. Bone marrow aspiration and core biopsy revealed a hypercellular bone marrow with increased numbers of unidentified blast cells and bizarre megakaryocyte proliferation. Circulating microfilariae were not present in the blood, but serum examined by immunofluorescence was strongly positive for antibodies against Dirofilaria immitis microfilariae. A diagnosis of myeloproliferative disease with megakaryocytic predominance and occult dirofilariasis was made.
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PMID:Myeloproliferative disease with megakaryocytic predominance in a dog with occult dirofilariasis. 1531 76

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

An aged male rhesus macaque in our colony had decreased appetite and a loss of interest in behavioral testing. CBC analysis revealed a regenerative, microcytic, hypochromic anemia with thrombocytosis, consistent with iron deficiency. A fecal occult blood test was positive. Ultrasound imaging revealed numerous, vascularized focal liver lesions that suggested metastases. The macaque's appetite continued to decrease, and he became more lethargic. At this point, the investigator elected to euthanize the macaque. At necropsy, the ileocolic junction was white and abnormally thickened, and the liver was pale tan with approximately 18 discrete white masses randomly scattered throughout the hepatic parenchyma. Histologically, the mass at the ileocolic junction was identified as an intestinal adenocarcinoma, whereas the liver masses were confirmed to be undifferentiated hepatic sarcomas. This case report describes a rhesus macaque that had 2 unrelated primary neoplasms. A review of the literature indicates that this rhesus macaque is the first reported to have an adenocarcinoma of the ileocolic junction and multiple hepatic sarcomas simultaneously.
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PMID:Adenocarcinoma of the ileocolic junction and multifocal hepatic sarcomas in an aged rhesus macaque (Macaca mulatta). 2420 73

A 2 yr old spayed female mixed-breed Irish wolfhound was referred for assessment of anemia and slowly progressing abdominal distention. At the time of admission, the dog had marked anemia and thrombocytosis, a decreased serum iron concentration, and a normal coagulation profile. An ultrasound examination showed a massive fluid-filled cavitated structure in the abdominal cavity. Paracentesis of that structure yielded a large amount of hemorrhagic fluid with an iron concentration >24 times greater than the serum iron concentration, consistent with chronic sequestration of iron, leading to iron-deficiency anemia. Blood transfusions and incomplete surgical removal of the structure allowed short-term stabilization of the patient, but the dog was euthanized 17 days postsurgery for lethargy and continued abdominal distention. Histopathological evaluation of the structure was consistent with a chronic expanding hematoma. To the authors' knowledge, this is the first reported case of intra-abdominal chronic expanding hematoma in a dog. It is also unique given its features of iron-deficiency anemia caused by internal blood loss.
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PMID:Abdominal chronic expanding hematoma causing iron-deficiency anemia in a dog. 2502 35

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity triggered by food proteins. It may present acutely, with repetitive vomiting, diarrhoea and lethargy leading to dehydration and eventually shock or insidiously with intermittent emesis, chronic diarrhoea or failure to thrive. We describe a paediatric male patient with recurrent sepsis-like episodes of fever, lethargy, ashen-grey skin colouration and vomiting followed by diarrhoea. These episodes were triggered by cow's milk formula and grains. Laboratory tests revealed leucocytosis, thrombocytosis, metabolic acidosis and elevated C reactive protein. After exclusion of other differential diagnoses, the diagnosis of FPIES was established on clinical improvement with withdrawal of the offending food and positive oral food challenge. FPIES diagnosis requires a high index of suspicion and is frequently delayed, which contributes to an increased morbidity. This is due to the wide spectrum of clinical presentations and due to the absence of specific diagnostic tests.
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PMID:Food protein-induced enterocolitis syndrome: a challenging diagnosis. 2943 5

Food protein-induced enterocolitis syndrome (FPIES) is a poorly understood non-IgE gastrointestinal-mediated food allergy that predominantly affects infants and young children. Cells of the innate immune system appear to be activated during an FPIES reaction. Acute FPIES typically presents between one and 4 hours after ingestion of the trigger food, with the principal symptom being profuse vomiting, and is often accompanied by pallor and lethargy. Additional features can include hypotension, hypothermia, diarrhoea, neutrophilia and thrombocytosis. In Australia, the most commonly reported foods responsible for FPIES are (in descending order) rice, cow's milk, egg, oats and chicken. Most children with FPIES react to only one food trigger, and thus, avoidance of multiple foods is often not indicated. FPIES is often misdiagnosed as sepsis or gastroenteritis. However, a diagnosis of FPIES is favoured if there is rapid resolution of symptoms within hours of presentation, an absence of fever, and a lack of a significant rise in C-reactive protein at presentation. Diagnosis is often hampered by the lack of awareness of FPIES, absence of reliable biomarkers, the non-specific nature of the presenting symptoms, and the delay between allergen exposure and symptoms. Although some national peak allergy bodies have attempted to improve the diagnosis and management of FPIES, up until 2017 there were no internationally agreed guidelines for its diagnosis and management.
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PMID:Food protein-induced enterocolitis syndrome: guidelines summary and practice recommendations. 3065 96