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)

(1) The concentrations of unconjugated and conjugated phenol, p-cresol, benzyl alcohol, catechol, hydroquinone, homocatechol, and 2-methoxyresorcinol in uremic serum were determined using a mass fragmentographic method. Concentrations of all phenols in uremic serum were higher than in normal serum. Conjugated phenols existed mainly as sulfate esters. (2) The concentration of unconjugated phenol in uremic serum correlated with those of serum creatinine and urea, but not with the hematocrit value. Patients with the highest concentration of unconjugated phenol suffered from cerebral disorders, coma or lethargy, and hemorrhagic tendencies. Unconjugated phenol was detected in normal serum at a concentration of 0.86 +/- 0.63 mumol/l (mean +/- S.D., n = 10). (3) The concentration of unconjugated p-cresol in uremic serum did not correlate with those of serum creatinine, urea and the hematocrit value. (4) The concentrations of unconjugated and conjugated hydroquinone in uremic serum correlated with those of serum creatinine and urea. (5) 2-Methoxyresorcinol was first detected mainly as sulfate ester in uremic serum at a concentration of 19 +/- 9.0 mumol/l (mean +/- S.D,. n = 17). (6) The daily excretion of eight unconjugated phenols into normal urine was determined.
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PMID:A gas chromatographic-mass spectrometric analysis for phenols in uremic serum. 721 14

Studies with unanesthetized active (non-lethargic) marmots demonstrated circannual rhythms of renal function (clearances of p-aminohippurate, creatinine, and inulin), plasma osmolality, and plasma sodium and potassium concentrations. Effective renal plasma flow, glomerular filtration rate, the clearance of creatinine, and plasma potassium were highest in spring and lowest in the fall and winter. Plasma osmolality and plasma sodium concentrations tended to be highest during the winter months and lowest in the spring and summer. p-Aminohippurate excretion was shown to be a Tm-limited system.
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PMID:Circannual renal function and plasma electrolytes of the marmot. 724 3

11 adult female dogs were given periodic intravenous injections of uranyl nitrate [UO2(NO3)2 . 6H2O] to create a syndrome of chronic uremia. Initially, dogs usually received 2.0 mg/kg of uranyl nitrate; subsequent doses were generally less. After the initial injection, there was an abrupt fall in creatinine clearance and rise in plasma urea nitrogen. Low and relatively constant creatinine clearances (10.2 +/- SD 2.7 ml/min) were easily maintained with further injections. Dogs developed proteinuria, aminoaciduria, weight loss, and plasma amino acid levels similar to those of chronically uremic humans and rats. With creatinine clearances of 4 ml/min or less, dogs became listless and lethargic, and daily activity and food intake decreased. Repeated injections of uranyl nitrate appear to be an easy and reliable method for creating a model of chronic uremia in dogs.
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PMID:Chronic uremia syndrome in dogs induced with uranyl nitrate. 736 Feb 99

Adult female mink (Mustela vison) were fed a diet that contained Fusarium moniliforme culture material that provided dietary concentrations of 89 ppm fumonisin B1, 21 ppm fumonisin B2, and 8 ppm fumonisin B3 for 87 days. During the trial, there was mild lethargy in the mink fed fumonisins, but no other clinical signs or differences in feed consumption (measured during the first two weeks), body weights, or survivability were observed between the fumonisin-treated and control mink. Several hematologic parameters (mean corpuscular hemoglobin concentration, plasma total solids, and lymphocyte concentration) and serum chemical concentrations (globulin, phosphorus, potassium, blood urea nitrogen, creatinine, bilirubin, and cholesterol) and activities (alkaline phosphatase, alanine aminotransferase, amylase, and aspartate aminotransferase) were greater in the mink fed fumonisins than in the controls. Serum albumin/globulin and sodium/potassium ratios and chloride concentrations were lower in the fumonisin-fed mink than in the controls. The concentrations of free sphinganine and the ratio of free sphinganine to free sphingosine in the liver and kidneys of the fumonisin-treated mink were greater than in the control mink. No histopathologic alterations were associated with fumonisin treatment. These results indicate that long-term dietary exposure to F. moniliforme culture material containing 118 ppm total fumonisins is not lethal to adult mink, but can produce adverse physiological effects in the animals.
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PMID:Chronic toxicity of fumonisins from Fusarium moniliforme culture material (M-1325) to mink. 757 84

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

One hundred fifty lactating mink on one ranch in southern Ontario were monitored over the lactation period in 1989 for evidence of clinical disease, and serial blood samples were collected for biochemical analysis. Antemortem blood samples were collected and necropsies performed on the 17 females that developed nursing disease and on 17 controls matched to the same stage of lactation and on ten nonlactating controls. Twenty-two additional nursing disease cases were selected from seven ranches in the following year and processed similarly. The clinical signs typically observed in affected females were sudden onset lethargy and anorexia followed by dehydration, ataxia, and a reluctance to move. The major clinical-pathologic findings were a marked increase in serum osmolality and total protein, urea nitrogen, creatinine, phosphorus, glucose, and potassium concentrations and a decrease in sodium and chloride concentration. In addition, the animals were acidotic, there was a reduction in the urine specific gravity, and the hemogram was consistent with a stress response. Emaciation and dehydration were the only pathologic changes consistently present in cases of nursing disease and not in controls. In almost all cases, bacteria were not cultured from the liver, spleen, and mammary gland, but Campylobacter jejuni was cultured from the intestinal contents of 15/17 affected mink and 2/5 controls. Aleutian disease virus antibody was not present in any of the affected mink. Lipid vacuoles in hepatocytes and renal tubular epithelium, hypertrophy of cells in the adrenal cortex, and pulmonary congestion and atelectasis were present in both diseased females and controls, as were various sporadic inflammatory lesions. Nursing disease may result from energy depletion due to lactation. All lactating females are affected by this process; clinical disease reflects the terminal physiologic decompensation of the most susceptible individuals.
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PMID:Nursing disease in mink: clinical and postmortem findings. 811 44

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.
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PMID:Osteopetrorickets. The paradox of plenty. Pathophysiology and treatment. 839 71

Two cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year-old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulness of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults.
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PMID:Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children. 843 72

We refer in the present article, the first case found in our laboratory of Monoclonal gammapathy of the IgD type. A 47-year-old man presented at the emergency department with a history of malaise, lethargy, tiredness, thirstiness and obscure depositions. Clinical examination revealed a normocytic anaemia. The plasma urea was 423 mg/dl and the plasma creatinine was 15, 3 mg/dl. He was admitted to hospital with a diagnosis of acute renal failure. The later electrophoresis in serum revealed a little monoclonal band that was identified as IgD-lambda type by immunofixation electrophoresis. In urine electrophoresis was observed a beta-band. Bone marrow biopsy revealed a 20% of plasmocytic cells. Renal biopsy was compatible with myelomatose lesions. Osteolytic lesions were observed.
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PMID:[A case of monoclonal gammapathy type IgD]. 901 14

The toxicity of ISIS 2302, a phosphorothioate oligonucleotide with antisense activity against human ICAM-1 mRNA, was investigated in cynomolgus monkeys (young adult). The oligonucleotide was administered by slow bolus injection every other day for 28 days (14 doses) at dose levels of 0, 2, 10, and 50 mg/kg/injection. The basic group size consisted of three male and three female monkeys which were sacrificed 2 days after the last dose. An additional 2 monkeys/sex in the vehicle control and 50 mg/kg dose groups remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, however, one monkey in the 10 mg/kg dose group was markedly lethargic after the first dose. Other clinical observations included periocular swelling (> or = 10 mg/kg) on the first day of the study, and bruising in all dose groups throughout the study. Bruising was associated with a dose-dependent prolongation of clotting times, particularly activated partial thromboplastin times (APTT), that was transient in nature. Bruises occurred around site of intravenous dosing or blood collection, and were manifested as subcutaneous hemorrhages upon microscopic evaluation. There were no corresponding alterations in hematology parameters including RBC or platelet counts. Other treatment-related microscopic alterations noted were intracytoplasmic eosinophilic granules and vacuolation in proximal tubular epithelial cells at 10 and 50 mg/kg, with free RBC in renal proximal tubular lumens at 50 mg/kg. Serum chemistry parameters including BUN and creatinine levels were normal in all dose groups and there were no notable alterations in urinalysis parameters. Granules and vacuolations in kidneys were reversed following a 4-week treatment free period. In general, 10 and 50 mg/kg ISIS 2302 produced dose-dependent changes in clotting times and the kidney that were reversible, while 2 mg/kg ISIS 2302 produced no remarkable alterations.
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PMID:Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a four-week study in cynomolgus monkeys. 918 1


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