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)

The effect of o,p'DDD therapy on the endogenous plasma ACTH concentration was evaluated in 15 dogs with hypophysis-dependent hyperadrenocorticism. Adequate control of hyperadrenocorticism with o,p'DDD was based on the reduction of water consumption to within the normal range, disappearance of clinical signs of lethargy, weakness, alopecia, thin skin, or pendulous abdomen, and an increase in blood cortisol below the normal range after exogenous ACTH administration. Endogenous ACTH concentrations were determined for each dog after the disease was controlled and while they were given o,p'DDD on a maintenance schedule. Endogenous ACTH concentrations increased in 14 of 15 dogs after o,p'DDD therapy, indicating a lack of suppressive effects of o,p'DDD on hypophysis ACTH secreting cells.
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PMID:Effect of o,p'DDD therapy on endogenous ACTH concentrations in dogs with hypophysis-dependent hyperadrenocorticism. 299 29

A 3-day-old girl had a syndrome of lethargy and lactic acidosis. Pregnancy and delivery had been normal; there was no consanguinity or family history of neuromuscular disease. At age 4 1/2 months, she had generalized weakness, hypotonia, areflexia, and macroglossia. She developed cyanosis and respiratory failure, and marked cardiomegaly was noted. She died at age 8 1/2 months of cardiac arrest. Results from a muscle biopsy specimen obtained at age 4 1/2 months showed ragged-red fibers and increased glycogen and lipid droplets. With the cytochrome c oxidase reaction, only 5% of the fibers stained positively in the biopsy specimen. Cytochrome c oxidase activity was 7.3% of normal in muscle mitochondria and 12.2% of normal in heart mitochondria. Reduced-minus-oxidized cytochrome spectra showed lack of the cytochrome aa3 peak. Immunotitration using antibodies against purified human heart cytochrome c oxidase showed normal amount of cross-reacting material in both heart and muscle. The genetic error could have involved a cytochrome c oxidase isozyme common to heart and muscle.
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PMID:Myopathy and fatal cardiopathy due to cytochrome c oxidase deficiency. 302 95

Two trials of CF-FUra in patients with metastatic colorectal cancer were performed, both using a 3 day loading dose and then weekly maintenance doses to minimize toxicity. The first trial used CF by IV infusion with constant dose of FUra 400 mg/m2, and the second trial used oral CF with escalating doses of FUra. In the first trial, 45 eligible patients (20 with and 25 without prior therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing 5FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. Objective responses were seen in 36% and stabilization of disease in 31% of patients, and correlated with prolonged survival. Median survival was 8 months for patients with prior treatment and 10 for those without, and 12 month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival. The second trial was recently conducted in cooperation with Duke University to determine toxicity and efficacy of oral CP with IV FUra prior to a randomized trial of this combination versus placebo with IV FUra. Eighteen patients were treated and serum levels of folates were obtained on 10. First toxicity occurred at FUra doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in 9, lethargy in 7, nausea/vomiting in 4, dermatitis in 4, conjunctivitis in 2, hypersalivation in 2, stomatitis in 1, and profound granulocytopenia in 1. Response rate was 35% and stabilization was 35% with median survival of 14 months and 12 month survival of 56%.
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PMID:Clinical experience with CF-FUra. 307 55

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.
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PMID:A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. 309 8

The divalent cationic ionophore A23187 (calimycin) facilitates the transport of calcium ions across biological membranes, resulting in an increase of cytosolic calcium. A23187 has been used extensively in vitro to activate calcium-dependent neurocellular processes. Because of its potential usefulness as a neurotoxicological probe, our laboratory conducted a series of studies to characterize the neurofunctional consequences of A23187 in the intact organism. In addition to approximating the LD50, the effects of acute parenteral administration of A23187 on conditioned avoidance, nociceptive shock threshold, open-field activity, consummatory behavior, body temperature and neuromotor function, including general activity, coordination, balance and grip strength, were assessed in the rodent. The LD50 of A23187, administered intraperitoneally to adult male rats, was 9.2 mg/kg. The predominant overt signs of toxicity included lethargy, limb weakness and apnea. Lower doses, from 0.5 to 0.03 mg/kg, produced a variety of more subtle neurobehavioral effects, including a selective depression of motor activity, a moderate elevation of shock threshold, altered conditioned avoidance behavior and hypothermia.
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PMID:Neurobehavioral effects of the calcium ionophore A23187. 311 83

A 12-year-old girl presented with weakness, diplopia, and lethargy after a prodrome of gastroenteritis. Laboratory studies were compatible with a diagnosis of hemolytic uremic syndrome. She developed seizures that were controlled by diphenylhydantoin and valium. In spite of peritoneal dialysis and fresh frozen plasma infusions, she progressed to a left hemiplegia associated with a brain scan finding of decreased blood flow in the right middle cerebral artery perfusion area. A 5 liter whole blood exchange transfusion did not improve the neurological status or low platelet count. Daily plasma exchanges with fresh frozen plasma replacement resulted in normal platelet count within 48 hours and was followed by progressive improvement in neurological status. Platelet agglutinating factor decreased to control levels. A repeat brain scan was normal.
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PMID:Reversal of central nervous system involvement in hemolytic uremic syndrome by use of plasma exchanges. 311 70

The electrophysiologic effects and antiarrhythmic efficacy of flecainide were evaluated by electrophysiologic study (EPS) in 20 patients with ventricular tachycardia (VT) refractory to an average 2.9 drugs. In 19 patients EPSs were performed with patients not receiving antiarrhythmic medications and receiving oral flecainide therapy at steady state (mean dose, 235 +/- 67 mg/day). Flecainide significantly increased the QRS complex duration (27%, P less than .001), PR interval (17%, P less than .001), and right ventricular effective refractory periods 8.5% and 21.1% (P less than .01) for the first and second extrastimuli, respectively. During baseline EPS, 17 patients were induced into VT and two were noninducible. Flecainide prevented EPS-induced VT in five patients and the induced VT became slow and hemodynamically stable in three. Two patients who failed flecainide monotherapy were induced into slow hemodynamically stable VT with flecainide in combination with amiodarone. The two noninducible patients, during baseline EPS, had suppression of spontaneous VT with flecainide. Overall, 13 of 20 patients received flecainide either alone or in combination with amiodarone for chronic therapy. Side effects encountered during the study consisted of blurred vision, dizziness, weakness, lethargy, nausea, worsened heart failure and bradyarrhythmias. After a mean 9-month follow-up (3 to 16 months) nine patients remain on flecainide therapy. There were three recurrences of slow, hemodynamically stable VT and no episodes of sudden death. Low-dose flecainide, either alone or in combination with other agents, is effective therapy for certain patients with refractory VT but heart failure remains a significant concern in patients with depressed left ventricular function.
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PMID:Clinical and electrophysiologic effects of flecainide in patients with refractory ventricular tachycardia. 312 56

Gram-negative neonatal septicemia was diagnosed in a premature Standardbred colt. Clinical signs included lethargy, weakness, loss of suckle reflex, tachypnea, and injected mucous membranes. Sequelae included pneumonia, omphalophlebitis, septic arthritis, and osteomyelitis. Prepartum maternal uterine infection, premature delivery, abnormal parturition with premature fetal membrane separation, and failure of passive transfer of colostral immunoglobulins increased the foal's risk for developing sepsis. Treatment included administration of moxalactam disodium and cefadroxil. The clinical efficacy of cephalosporin antibiotics in the treatment of gram-negative sepsis is discussed.
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PMID:Omphalophlebitis and osteomyelitis associated with Klebsiella septicemia in a premature foal. 320 51

Patients with agammaglobulinemia are particularly susceptible to chronic enteroviral infections of the central nervous system. Data on 42 patients were obtained by literature review, communications with other physicians, and personal experiences. Thirty-eight patients had congenital immunodeficiencies, most frequently X-linked agammaglobulinemia. Most patients who could be assessed were receiving maintenance therapy with intramuscular gamma-globulin before their enteroviral infection. Seven patients had not been recognized as hypogammaglobulinemic before the onset of infection. The commonest pathogens were echoviruses (37 of 41 cases), especially type 11 (11 cases). Thus far, four patients have had sequential or simultaneous infections with a second enteroviral serotype. Other features of the disease have included weakness, lethargy or coma, headaches, hearing loss, seizures, ataxia, and paresthesias. Some patients have also had nonneurologic manifestations of chronic enteroviral infection, including fever, the dermatomyositis-like syndrome, edema, rashes, and hepatitis. Treatment has consisted primarily of antibody administration, either in intravenous immunoglobulin preparations or in immune plasma. Twelve patients have received intraventricular immunoglobulin through reservoir devices; six of these 12 have improved substantially, as judged by clinical criteria.
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PMID:Chronic enteroviral meningoencephalitis in agammaglobulinemic patients. 329

The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.
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PMID:Organophosphate and carbamate poisoning in infants and children. 333 78


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