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)

Two from a group of approximately 50 C.B-17 scid-bg mice were examined because of lethargy, dehydration, and rough coat. Three months prior to development of clinical signs of disease, mice of this study had been surgically implanted with fetal bovine liver, thymus, and lymph node. At necropsy, marked splenomegaly and mild hepatomegaly were observed in both animals. Large areas of necrosis and inflammation, with associated intracytoplasmic granular basophilic inclusions, were observed in histologic sections of multiple organs. Aerobic and anaerobic culturing of the liver yielded negative results. Six months after the initial case, four more reconstituted scid-bg mice from a different fetal donor had identical clinical, gross, and histologic signs of disease. To determine whether the basophilic inclusions represented an infective agent, 4-month-old immune-naive C.B-17 scid-bg mice were inoculated intraperitoneally with a liver and spleen homogenate from an affected mouse. Two weeks after inoculation, mice developed clinical signs of disease and lesions identical to those seen in the signal mice. On ultrastructural examination of the liver, pleomorphic bacteria were found in large cytoplasmic vacuoles of hepatocytes. Bacterial DNA was amplified from the liver, using primers that amplify a segment of the 16S rRNA gene from many bacterial species. Sequencing of the polymerase chain reaction (PCR) product revealed gene sequence identical to that of Coxiella burnetii, the agent of Q-fever. These results highlight the need to consider infective agents of the donor species when working with xenografted animals.
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PMID:Coxiella burnetii infection in C.B-17 scid-bg mice xenotransplanted with fetal bovine tissue. 1192 95

Forty-six cats with clinical haemobartonellosis were studied; 75 per cent of the cats of known age were two-and-a-half years old or younger, 50 per cent were intact males and 19.5 per cent were castrated males. The predominant signs of the disease were tachypnoea, lethargy, depression, anorexia, infestation with fleas, pale mucous membranes, icterus, emaciation, dehydration, splenomegaly, anaemia, leucocytosis, increased activities of alanine aminotransferase and aspartate aminotransferase, and azotaemia. Thirty-eight per cent of the cats that were tested for feline leukaemia virus (FeLV) antigen were positive, and 22 per cent of those tested for feline immunodeficiency virus (FIV) antibodies were positive. The prevalence of both FeLV and FIV was much higher than in the general Israeli cat population. The cats infected with both Haemobartonella felis and FeLV had a significantly lower body temperature, were more anaemic and the mean cell volume of their erythrocytes was greater than in the cats with haemobartonellosis alone.
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PMID:Retrospective study of 46 cases of feline haemobartonellosis in Israel and their relationships with FeLV and FIV infections. 1216 25

A 2.5-year-old spayed female German Shepherd Dog was referred for evaluation of progressive anemia, lethargy, and weight loss. Seventeen days earlier, the dog had received a whole blood transfusion to manage hemorrhage after ovariohysterectomy. Mild fever, splenomegaly, and thrombocytopenia were also identified. Von Willebrand disease and Babesia gibsoni infection were diagnosed. Because of the serologic cross-reactivity of B gibsoni and B canis in the immunofluorescent antibody assay for IgG antibodies against these organisms, polymerase chain reaction amplification of parasite DNA was required to identify the infecting Babesia sp. The source of the B gibsoni infection was traced to an apparently healthy American Pit Bull Terrier blood donor. Despite resolution of clinical signs in the dog of this report, a series of antiparasitic treatments failed to eliminate the B gibsoni infection. Screening of potential blood donor dogs for Babesia spp is becoming increasingly important in the United States.
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PMID:Transfusion-associated Babesia gibsoni infection in a dog. 1268 86

N,N-Dimethylaniline is used as a chemical intermediate in the synthesis of dyestuffs. Toxicology and carcinogenesis studies were conducted by administering N,N-dimethylaniline (greater than 98% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 2 weeks, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse lymphoma cells, and Chinese hamster ovary (CHO) cells. Two-Week and Thirteen-Week Studies: In the 2-week studies, doses were 94-1,500 mg/kg; deaths of rats and mice were observed in groups given doses of 750 or 1,500 mg/kg. The final mean body weights of male rats that received 375 or 750 mg/kg were 15% or 47% lower than that of vehicle controls; final mean body weights of other groups of rats and mice were similar to those of vehicle controls. Compound-related clinical signs observed included cyanosis in rats and lethargy and tremors in rats and mice. Splenomegaly occurred in nearly all dosed groups of rats and mice, and the incidences were dose related. In the 13-week studies, doses were 32-500 mg/kg; no compound-related deaths occurred. The final mean body weights of male rats that received 250 or 500 mg/kg were 15% or 27% lower than that of vehicle controls. The final mean body weights of all groups of dosed female rats and male and female mice were within 12% of those of vehicle controls. Compound-related clinical signs included lethargy in rats and mice and cyanosis in rats. Splenomegaly was observed in all dosed groups of rats and mice; the severity was dose related. Compound-related extramedullary hematopoiesis and hemosiderosis occurred in the kidney or testis of dosed rats and liver and spleen of dosed rats and mice. Two-year studies were conducted by administering 0, 3, or 30 mg/kg N,N-dimethylaniline in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 rats of each sex. The lower dose was selected to be one-tenth the higher dose to increase the likelihood that one dose would cause only a minimal nonneoplastic response. Groups of 50 mice of each sex were administered 0, 15, or 30 mg/kg on the same schedule. Body Weight and Survival in the Two-Year Studies: Mean body weights of vehicle control and dosed rats and mice were similar throughout the studies. Survival rates of all respective groups were similar after 2 years, except for the lowered survival of vehicle control female rats (vehicle control, 21/50; low dose 32/50; high dose, 36/50). This may reflect the large number (24/50) of vehicle control female rats killed when observed to be in a moribund state. Final survival for other groups was as follows: male rats--29/50; 32/50; 28/50; male mice-- 34/50; 30/50; 34/50; female mice--35/50; 39/50; 33/50. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: In these 2-year studies, the spleen was the expected site of chemical-related effects. Fatty metamorphosis and fibrosis in the spleen of high dose male rats were increased (fatty metamorphosis: vehicle control, 0/49; low dose, 1/49; high dose, 10/50; fibrosis: 5/49; 2/49; 22/50). Splenic hemosiderosis and hematopoiesis were present at an incidence greater than 85% in all groups of rats; however, the severity of the lesions was greater in dosed groups than in vehicle controls. Sarcomas of the spleen were seen in 3/50 high dose male rats, and an osteosarcoma was seen in another high dose male rat. One additional high dose male rat had a sarcoma of the thymus. Splenic sarcomas are uncommon in corn oil vehicle control male F344/N rats (NTP historical incidence 3/2,081, 0.1%), and thus, these neoplasms in high dose male rats (4/50, 8%) were considered to be chemically related. Lower incidences of mononuclear cell leukemia (which apparently originates in the spleen) were seen in dosed male and female rats than in vehicle controls (male: 13/50; 4/50; 3/50; female: 11/50; 7/50; 0/50). The incidence of squamous cell papillomas of the forestomach in high dose female mice was marginally greater than that in vehicle controls (2/50; 2/50; 8/50). No malignant forestomacin vehicle controls (2/50; 2/50; 8/50). No malignant forestomach neoplasms were observed. Genetic Toxicology: N,N-Dimethylaniline was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of exogenous metabolic activation. In the mouse lymphoma assay, N,N-dimethylaniline produced a positive response with and without metabolic activation. In CHO cells, N,N-dimethylaniline induced both sister chromatid exchanges (SCEs) and chromosomal aberrations in the presence of exogenous metabolic activation. Without activation, an increase in chromosomal aberrations was observed, but no increase in SCEs occurred. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of N,N-dimethylaniline for male F344/N rats, as indicated by the increased incidences of sarcomas or osteosarcomas(combined) of the spleen. There was no evidence of carcinogenic activity of N,N-dimethylaniline for female F344/N rats given 3 or 30 mg/kg body weight by gavage for 2 years. There was no evidence of carcinogenic activity of N,N-dimethylaniline for male B6C3F1 mice given 15 or 30 mg/kg body weight by gavage for 2 years. There was equivocal evidence of carcinogenic activity of N,N-dimethylaniline for female B6C3F1 mice, as indicated by an increased incidence of squamous cell papillomas of the forestomach. Both rats and mice could have tolerated doses higher than those used in these studies. There were decreased incidences of mononuclear cell leukemia in dosed male and high dose female rats. Compound-related splenic fibrosis, hemosiderosis, and fatty metamorphosis were increased in male rats. Synonyms: dimethylaminobenzene; N,N-dimethylbenzeneamine; dimethylaniline; dimethylphenylamine; N,N-dimethylphenylamine
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PMID:Toxicology and Carcinogenesis Studies of N,N-Dimethylaniline (CAS No. 121-69-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 81

A 13-year-old neutered male Jack Russell Terrier (Parson Russell Terrier) was presented to the Texas Veterinary Medical Center with a history of lethargy, depression, vomiting, and fever. The dog had mildly regenerative anemia, severe thrombocytopenia and low antithrombin activity. Marked splenomegaly was found on physical examination and imaging studies, and malignant round cell neoplasia and marked extramedullary hematopoiesis were diagnosed on aspirates of the spleen. The dog underwent exploratory laporatomy and splenectomy. Because of a rapid decline in clinical condition postsurgery, the dog was euthanized. Splenic and hepatic biopsies were submitted for histopathologic evaluation. A neoplastic population of round cells was found throughout the splenic parenchyma and within hepatic sinusoids. The neoplastic cells stained strongly positive for CD3 (T-cell marker) and were negative for CD79a (B-cell marker) and lysozyme (histiocytic marker). A diagnosis of T-cell lymphoma was confirmed by assessment of T-cell clonality using canine-specific polymerase chain reaction-based techniques. Although expression of the gammadelta T-cell receptor was not evaluated, this case shares many similarities with a rare syndrome in humans known as hepatosplenic gammadelta T-cell lymphoma.
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PMID:Morphologic, immunohistochemical, and molecular characterization of hepatosplenic T-cell lymphoma in a dog. 1519 70

A retrospective study was performed at the Department of Clinical Sciences of Companion Animals at Utrecht University amongst 75 dogs diagnosed with a Babesia canis and/or an Ehrlichia canis infection. The majority of the dogs had visited an endemic area (most often the Mediterranean area or the Dutch Antilles), but two dogs became infected with Babesia in the Netherlands. Babesia infections were associated with a stay in an endemic area and an incubation period that are both significantly shorter (less than 3 months) than those for Ehrlichia and co-infections (more than 3 months). Reasons for the owner to seek veterinary attention (lethargy, anorexia, fever), findings from the physical examination (pale mucous membranes, hepato-/splenomegaly) and laboratory results (anemia, thrombocytopenia, hypo-albuminemia) were highly aspecific, making serology or PCR mandatory for diagnosing infections. Antigenic stimulation by the parasite sometimes resulted in immune-mediated diseases such as immune-mediated hemolytic anemia, thrombocytopenia, glomerulonefritis, and polyarthritis and in the case of ehrlichiosis in hypergammaglobulinemia. Specific therapy (imidocarb-diproprionate and/or doxycycline) was necessary, and because combined infections were common, it was considered appropriate to administer both drugs while the definitive diagnosis was being established. The prognosis was reasonably good, with almost half of all patients showing no clinical signs after treatment, although Babesia and co-infections were associated with a significantly longer survival sometimes resulted than Ehrlichia infections.
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PMID:[Ehrlichia and Babesia infections in dogs in The Netherlands]. 1562 93

A 7-year-old, intact male Dachshund was presented to the Lyon veterinary school for lethargy and anorexia of several weeks duration. The main clinical signs were pale and icteric mucous membranes, hepatomegaly, splenomegaly, and lymphadenopathy. Results of a CBC and plasma biochemistry tests revealed severe nonregenerative anemia, thrombocytopenia, and increased alanine aminotransferase and alkaline phosphatase activities. Blood smear evaluation and cytologic examination of lymph node and bone marrow aspirate specimens revealed a large population of poorly differentiated blast cells with morphologic features suggesting megakaryocytic lineage. A low number of well-differentiated but dysplastic megakaryocytes also were observed in lymph node and bone marrow smears. A few blast cells were erythrophagocytic. Blast cells were positive for glycoprotein IIIa, factor VIII-related antigen, and factor XIII using immunocytochemistry. The dog was euthanized and necropsied. Histologic findings consisted of diffuse, massive infiltration of lymph nodes, liver, and spleen by megakaryoblasts and atypical megakaryocytes, with widespread thrombosis. This case confirms the usefulness of immunochemistry, including for factor XIII, in the diagnosis of megakaryoblastic leukemia, and demonstrates the unique features of tumor cell erythrophagocytosis and marked fibrinous thrombosis, which have not been reported previously in dogs.
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PMID:Acute megakaryoblastic leukemia with erythrophagocytosis and thrombosis in a dog. 1573 19

Cases of disseminated Mycobacterium avium infections in dogs are rare because it appears that the species is innately resistant to infection. A 2-year-old, castrated, 5 kg Shih Tzu-Poodle-cross developed anemia, abdominal pain, lethargy, and splenomegaly. Histological examination of surgically removed spleen indicated marked granulomatous splenitis with myriad intracytoplasmic acid-fast bacterial rods. Ultrastructural examination revealed the presence of 3-4-microm-long mycobacteria in phagolysosomes of epithelioid macrophages. Tissue extract of lightly fixed spleen was positive for M. avium 16S ribosomal RNA and negative for M. tuberculosis complex IS6110 DNA by polymerase chain reaction testing. Anemia was associated with the presence of mycobacteria-infected macrophages in bone marrow. The animal's condition deteriorated, and euthanasia was performed after a clinical course of 2 months. The principal morphological findings at necropsy were severe diffuse granulomatous hepatitis, enteric lymphadenomegaly, and segmental granulomatous enteritis with intralesional mycobacteria present. Mycobacterium avium was cultured from enteric lymph nodes sampled at necropsy. The source of infection was not established but was presumed to be environmental with an enteric portal of entry.
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PMID:Fatal mycobacteriosis with hepatosplenomegaly in a young dog due to Mycobacterium avium. 1582 7

A frail 78-year-old man presented with lethargy, fever, splenomegaly and pancytopenia. Bone marrow aspirate showed marked haemophagocytosis. A diagnosis of haemophagocytic syndrome secondary to diffuse splenic large B-cell lymphoma was eventually made. Treatment with laparascopic splenectomy was successful. Secondary haemophagocytic syndrome is a rare complication of many common conditions, and is fatal if untreated. A brief literature review is included.
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PMID:Non-fatal haemophagocytic syndrome in an elderly patient. 1610 62

Clinical observations of Babesia canis infection in 63 dogs during a 1-year period are summarised, demonstrating the pathogenicity of the Babesia strain endemic in Hungary. Most patients had babesiosis in the spring and autumn, correlating with the seasonal activity of ticks. Male animals appeared in higher numbers, probably due to an overrepresentation of outdoor dogs. Uncomplicated babesiosis was diagnosed in 32 cases. The disease affected dogs of any age in this study. Symptoms were similar to those published from other parts of the world: lethargy, fever, splenomegaly, pallor, icterus, haemoglobinuria and presence of ticks were the most common observations. Thrombocytopenia, lymphopenia and neutropenia were frequent haemogram changes. Imidocarb appeared to be highly effective in eliminating the Babesia infection. Thirty-one animals demonstrated babesiosis with complications. Most Rottweilers (7/9) developed complicated disease. Old age was a risk factor for multiple complications. Multiple organ manifestations had poor prognosis. Hepatopathy (44%), pancreatitis (33%), acute renal failure (ARF; 31%) and disseminated intravascular coagulation (DIC; 24%) were frequent complications, while immune-mediated haemolytic anaemia (IMHA; 10%), acute respiratory distress syndrome (ARDS; 6%) and cerebral babesiosis (3%) were rarely observed. There was a significant difference between the mean age of dogs having uncomplicated disease, babesiosis with a single complication and babesiosis with multiple complications (3.4, 4.8 and 8.6 years, respectively, p < 0.001). The recovery rate (78, 68 and 25%, respectively, p = 0.005) and mortality rate (3, 21 and 67%, respectively, p < 0.001) also tended to differ significantly in these groups. Systemic inflammatory response syndrome (SIRS) and DIC are two possible pathways leading to multiple organ dysfunction syndrome (MODS) in babesiosis. DIC was found to predict MODS more sensitively in this study than SIRS: there were 6 animals developing MODS out of 11 identified with DIC, while only 5 dogs developed MODS out of 22 having SIRS.
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PMID:Clinical manifestations of canine babesiosis in Hungary (63 cases). 1702 Jan 40


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