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)

A patient who developed chronic salicylism associated with salicylate therapy for treatment of juvenile rheumatoid arthritis is described, and the clinical presentation and treatment of chronic salicylism are reviewed. A 5 1/2-year-old boy was receiving aspirin 150/mg/kg/day for treatment of juvenile rheumatoid arthritis. While on salicylate therapy, the patient developed tachypnea and became increasingly hyperthermic, lethargic, and disoriented. The patient developed a maculopapular rash, weakness, and a decreased level of consciousness during the 11 days before admission to the hospital. Physical examination and laboratory determinations revealed that the patient had hypoprothrombinemia, hypoglycemia, and severe hepatic encephalopathy secondary to long-term salicylate toxicity. The patient was treated for hypoglycemia, electrolyte imbalances, thrombocytopenia, and anemia and was discharged after 24 days. Diagnosing chronic salicylism with hepatic dysfunction was difficult because the symptoms are similar to those of stage I to stage II Reye's syndrome. Liver enzymes, including aspartate aminotransferase (also called SGOT), alanine aminotransferase (also called SGPT), alkaline phosphatase, and lactate dehydrogenase, may be elevated in juvenile arthritis patients with hepatic dysfunction. Liver dysfunction usually improves when salicylate therapy is discontinued. Supportive therapy should always be used in symptomatic patients. Children on long-term, high-dose salicylate therapy should be monitored closely, and baseline liver function tests should be performed. The clinical effectiveness of administering sodium bicarbonate in attempts to alkalinize urine and increase salicylate elimination is controversial. In patients with juvenile rheumatoid arthritis who develop chronic salicylism, careful analysis of the patient's medication history, laboratory values, and clinical presentation are necessary to rule out Reye's syndrome.
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PMID:Chronic salicylism in a patient with juvenile rheumatoid arthritis. 370 82

A case of infantile optic glioma involving the whole optic pathway is reported. The patient was a 4-month-old female. The mother noticed that the baby could not follow the object, although her physical development had been apparently normal only until three months after birth. On admission, she was lethargic, although no definite motor weakness was identified. The ophthalmological check revealed delayed bilateral pupillary light reaction and choked disks. Skull X-ray film showed the J-shaped sella and the enlarged bilateral optic canals. CT scan also revealed an isodensity mass in the suprasellar cistern and enlarged bilateral optic nerves. The lesions were enhanced homogeneously with contrast medium and extended toward both optic radiations. Lateral ventricles were mildly dilated. Cerebral angiography showed the upward shift of A1-portion of the bilateral anterior cerebral arteries and the backward shift of the basilar artery. No abnormal vessels were visible. A bifrontal craniotomy was performed to partially remove the suprasellar tumor. The histological diagnosis was optic glioma. The postoperative course was uneventful. The patient was discharged without any neurological deficits except poor visual acuity. Four months later, she suddenly fell into generalized convulsion. CT scan revealed the significant enlargement of residual tumor and ventricular dilatation. Surgical treatment of VP shunt was immediately performed on, and then irradiation of 4,000 rad of total dose to the tumor followed. The tumor size became definitively small. On a follow-up term of 15 months, the patient has been doing well.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Infantile optic glioma involving the whole optic pathway--a case report]. 372 75

This is the first report in which a marine mollusc, Oliva vidua fulminans (olives), generally not known to be poisonous, was responsible for death in five children after consuming boiled olives with tamarind. The onset of symptoms was rapid 10 to 20 min after consumption of the olives. Signs and symptoms included nausea, vomiting, abdominal pain, tingling sensation around the lips, numbness around the mouth, drowsiness, lethargy and generalized weakness with paraesthesia in the limbs. The five deaths occurred within 3 to 4 hours after eating the poisoned olives and resulted from respiratory failure. Left-over olives from the affected household and freshly collected live olives had a toxicity of 14,200 mouse units (M.U.) and 15,000 M.U. per 100 g meat respectively. No other common chemical poison and organophosphorus insecticides were detected. The neurotoxic agent was acid and heat stable and was toxic at pH less than 4. Its action was similar to that of paralytic shellfish poisoning which was caused by toxins from certain dinoflagellates.
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PMID:Oliva vidua fulminans, a marine mollusc, responsible for five fatal cases of neurotoxic food poisoning in Sabah, Malaysia. 372

Atherosclerosis was diagnosed on necropsy in 21 dogs in a 14-year period. Nine dogs died and 12 were euthanatized because of complications associated with the disease. The mean age was 8.5 +/- 0.5 years; 18 dogs were male. Three breeds (Miniature Schnauzer, Doberman Pinscher, and Labrador Retriever) had a higher prevalence of the disease than other breeds in the canine necropsy population of The Animal Medical Center. Most common clinical signs were lethargy, anorexia, weakness, dyspnea, collapse, and vomiting. Hypercholesterolemia, lipidemia, and hypothyroidism were common in affected dogs tested, and protein electrophoresis revealed high values for alpha 2 and beta fractions in all dogs tested. Electrocardiography indicated conduction abnormalities and myocardial infarction in 3 of 7 dogs. Necropsy revealed that affected arteries (including coronary, myocardial, renal, carotid, thyroidal, intestinal, pancreatic, splenic, gastric, prostatic, cerebral, and mesenteric) were yellow-white, thick and nodular, and had narrow lumens. Myocardial fibrosis and infarction also were observed in the myocardium. Histologically, affected arterial walls contained foamy cells or vacuoles, cystic spaces, mineralized material, debris with or without eroded intima, and degenerated muscle cells.
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PMID:Clinical and pathologic findings in dogs with atherosclerosis: 21 cases (1970-1983). 374 84

The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium-chain or long-chain enzyme activity in cultured skin fibroblasts or in leukocytes. Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro- or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains to be determined.
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PMID:Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome. 379 3

Tiazofurin is a novel C-nucleoside with significant antitumor activity in murine tumor models. In a phase I clinical trial, patients received tiazofurin by bolus iv infusion daily for 5 days. Six doses ranging from 550 to 4100 mg/m2/day were evaluated. Thirty-one treatment courses were initiated in 21 patients. Tiazofurin induced multiple, transient toxic effects at all but the lowest dose level, and treatment interruption was a common result. Nine of 28 treatment courses initiated at doses greater than or equal to 1100 mg/m2/day were interrupted at less than 5 days; only five of eight courses initiated at 1100 mg/m2/day were completed. Symptoms leading to treatment interruption included headache, nausea and emesis, and lethargy and malaise. Other significant, transient toxic effects included skeletal muscle injury manifest as pain, weakness, or serum biochemical abnormalities; mucocutaneous effects; and mental or mood changes. One case each of transient pericarditis and fatal cardiomyopathy occurred at the highest dose. Myelosuppression was observed but was transient and not dose limiting. In addition to leukopenia and thrombocytopenia, unexpected declines in serum hemoglobin were observed, although these were of uncertain significance. Tiazofurin induced significant increases in uric acid production which could be reversed with coadministration of allopurinol. Pharmacokinetic analysis revealed tiazofurin plasma elimination to be at least biphasic, with a beta-half-time of 4.2 hours; most of an injected dose could be recovered from the urine as unaltered compound within 24 hours. From this study we conclude that an appropriate dose for phase II trials with this schedule is less than or equal to 1000 mg/m2/day. The schedule may be a difficult one for clinical evaluation of antitumor activity, however, because of the possibility of frequent treatment interruption due to multiple systemic toxic effects.
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PMID:Phase I trial of tiazofurin administered by i.v. bolus daily for 5 days, with pharmacokinetic evaluation. 380 11

The authors report a case of erythromycin-induced carbamazepine toxicity in a 6-year-old child following use of erythromycin ethylsuccinate (50 mg/kg/day). Within 5 days of erythromycin use, vomiting, weakness, lethargy, ataxia, nystagmus, and cogwheeling movements developed. A serum carbamazepine concentration had increased from 11.9 mg/L (measured 1 week prior to antibiotic use) to 25.8 mg/L. Following erythromycin withdrawal, serum concentrations returned toward baseline, and symptoms resolved. Erythromycin has known effects on hepatic enzyme function, with altered cytochrome P-450 function. The dramatic reduction in carbamazepine clearance observed in this patient is similar to that reported when erythromycin is used concurrently with other drugs. A brief review of potentially significant erythromycin drug interactions is presented.
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PMID:Erythromycin-induced drug interactions. An illustrative case and review of the literature. 381 8

A Phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193, tiazofurin) was conducted using a 5-day continuous infusion schedule. Twenty-four patients with advanced cancer were entered on this trial. Dose levels ranged from 360 to 2350 mg/sq m/day for 5 days. Neurotoxicity was dose limiting and occurred in six patients. Neurotoxicity was expressed as confusion, lethargy, or obtundation and was associated with focal neurological deficits in four of six patients: hemiparesis, three; cortical blindness and bilateral upper extremity weakness, one. Neurotoxicity was not clearly dose related, occurring at 900 mg/sq m/day for 5 days (two patients), 1100 mg/sq m/day for 5 days (two patients), 1850 mg/sq m/day for 5 days, and 2350 mg/sq m/day for 5 days (one patient each). Other toxicities seen were myelosuppression, desquamation of palms and soles, malar erythema, and hyperpigmentation, stomatitis, chest pain, drug fever, and increased serum creatine phosphokinase. Administered drug [71.5 +/- 11.2% (SE)] was recovered intact in the urine within 24 h of administration. Terminal-phase mean harmonic half-life was 8.0 h. The unpredictable neurotoxicity seen following continuous infusion therapy with tiazofurin suggests that Phase II trials of this schedule are not indicated until better understanding of the biochemical effects of tiazofurin is achieved.
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PMID:Phase I clinical study with pharmacokinetic analysis of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193) administered as a five-day infusion. 398 12

A 49-year-old woman was admitted to Hacettepe Medical Faculty Hospital with the complaints of headache, nausea, vomiting, lethargy, and weakness on her right side. She revealed a history of pulmonary Cryptococcus infection 5 years before and she had been treated with amphotericin B. After clinical and laboratory investigation she was thought to have an intracranial mass, but her deteriorating situation did not allow any surgical intervention; she died within 7 days. On necropsy, hard, gray-white nodular pulmonary lesions, ranging 0.1-4 cm in diameter, basal meningitis, infarcts, and a nodular lesion 1.5 cm in diameter similar to those of the lung were present in the white matter of the right hemisphere of the brain. Microscopic examination revealed granulomatous inflammation caused by Cladosporium, which had brown pigment and septate hyphae.
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PMID:Cerebral cladosporiosis. 403 53

Toxic effects of 5-hydroxymethyldeoxyuridine (HMUdR) were studied in white Swiss mice. Pathological, hematological, and clinical chemistry parameters were examined. Systemic toxicity was not observed in mice after ip administration of HMUdR in single doses up to 2000 mg/kg. Mice administered HMUdR daily for 15 days at 200 mg/kg, ip, manifested loss of weight, rough hair coat, diarrhea, swollen abdomens, weakness, lethargy, and a 20% mortality rate. Hematological and clinical chemistry parameters of all mice receiving HMUdR were within normal limits. At necropsy, all organs were grossly normal but microscopic examination of tissues of treated mice revealed the presence of shortened, thickened villi in the small intestine, nuclear vacuolation and necrosis of intestinal crypt epithelial cells, and some cytoplasmic vacuolation causing nuclear margination in hepatocytes. All histological lesions were reversible with cessation of treatment. HMUdR was active against murine L1210 and L5178Y leukemias in cell culture. The concentrations required to inhibit cell growth 50% compared to untreated cells was 2 and 4 microM, respectively. When HMUdR was administered ip at 50, 100, or 200 mg/kg in five daily doses to mice implanted with L1210 cells, life spans increased 20, 30, or 33% over placebo-treated controls.
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PMID:Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine. 403 87


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