Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
 ...
PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations. Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis. Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific. Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common. Without maintenance therapy 50% of patients relapse; fluconazole is recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T. gondii serology is exceptional but positive serum titres are usually unhelpful. Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common. Appearances on CT scan or MRI may take several weeks to improve. The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify. Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended. A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.
 ...
PMID:Central nervous system opportunistic infections in HIV disease: clinical aspects. 134 47

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.
 ...
PMID:A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion. 142 28

The therapeutic efficacy and toxicity of alpha-interferon (alpha-IFN) (Roferon, Hoffmann-La Roche, Inc., Nutley, NJ) were determined in 15 children (age range, 6 to 20 years) with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML). All patients had received cytoreductive therapy with either hydroxyurea (n = 13) or busulfan (n = 1) or both (n = 1) for 6 weeks to 46 months (median, 7 months) before beginning alpha-IFN therapy at a dose of 5 x 10(6) U/m2/d intramuscularly. This dose was escalated to 10 x 10(6) U/m2/d if leukemia was inadequately controlled. Ten children had a hematologic response, with nine showing a reduction in the percentage of Ph+ marrow cells, including four who had no detectable Ph+ cells in marrow samples collected 48 to 204 weeks after the initiation of therapy. Two of 15 patients remain free of Ph+ cells. Therapy was discontinued before week 104 in ten patients because of the following: (1) early hematologic responses without a decrease in Ph+ cells (three patients); (2) early resistant disease (one patient); (3) blast crisis (one patient); (4) progressive disease (two patients); (5) seizure attributed to high-dose alpha-IFN (one patient); or (6) an inadequate trial of alpha-IFN caused by aseptic necrosis or poor compliance (two patients). The most common side effects were mild and have included fever, malaise, headache, myalgias, and pain at the injection site. Adverse events causing interruption of therapy were seizures, aseptic necrosis, and myelofibrosis. alpha-IFN stabilizes the chronic phase of Ph+ CML in some children, is adequately tolerated when administered at a dose of 2.5 to 5 x 10(6) U/m2/d intramuscularly, and results in a significant decrease in the proportion of Ph+ metaphases in some patients. alpha-IFN in combination with an effective cytoreductive agent or agents appears worthy of further clinical testing in this disease.
 ...
PMID:Response to alpha-interferon in children with Philadelphia chromosome-positive chronic myelocytic leukemia. 183 44

Even in the absence of clinically apparent seizures, patients undergoing chronic dialysis often exhibit abnormal EEG activity, which is usually attributed to the type of dialysis or to the dysequilibrium syndrome. To find out whether these abnormalities occurred only during dialysis sessions, 10 children with end-stage renal failure undergoing chronic dialysis were continuously monitored for 52 h during dialysis and between two sessions. The EEG tracing was abnormal in 5 children. Two had paroxysmal aspecific slow waves towards the end of the sessions, with a fall in blood pressure, malaise and fainting. In 3 children EEG abnormalities - also present in the interdialytic period - were not clinically apparent. Long-term EEG monitoring in these cases distinguished between the electrical events that were related to dialysis and those that were not. It also suggested that, rather than being dialysis-dependent, these events frequently reflect a basic neurological disorder.
 ...
PMID:Long-term EEG monitoring in uremic children on chronic dialysis treatment. 186 59

Three patients with hyponatremia were found at an residential home of mental developmental delay. Because pimozide had been administered to all of them, it was suggested that pimozide might have induced compulsive water drinking resulting in hyponatremia. To my knowledge, there has been no previous report that pimozide may induce hyponatremia. As children with mental developmental delay and/or autism frequently develop epilepsy, hyponatremia should be included in the differential diagnosis of convulsive seizures. Particularly when antipsychotic drugs such as pimozide have been given, we should pay attention to polydipsia, polyuria and/or general malaise and prevent hyponatremia.
 ...
PMID:[Three cases of hyponatremia during administration of pimozide]. 193 Nov 69

Two patients developed clinical and laboratory evidence of systemic lupus erythematosus (SLE) during treatment with valproate (VPA) preparations. The first patient, a 47-year-old man, had fever, malaise, and thrombocytopenia 1 month after VPA was added to phenytoin (PHT) and primidone (PRM). He developed high titers of antinuclear antibodies (ANA) and anti-DNA antibodies, and hypocomplementemia. After discontinuation of PHT and VPA, steroid and immunoglobulin treatment was required for 4 weeks before his condition improved. The second patient, a 28-year-old woman, had been followed for idiopathic leukopenia for 3 years and had previously experienced fever and lymphadenopathy from PHT. After 4 months of divalproex therapy, she developed confusion, joint pain, and a dramatic increase in seizure frequency. She also developed high titers of ANA and anti-DNA antibodies and hypocomplementemia, along with a further decrease in white blood cell (WBC) count. These responded to steroid therapy and withdrawal of divalproex. Three months later, reintroduction of divalproex was followed by a return of ANA in low titer, which resolved after discontinuation. We believe that VPA may have caused true SLE in these patients, one of whom was probably predisposed.
 ...
PMID:Possible induction of systemic lupus erythematosus by valproate. 211 70

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.
 ...
PMID:Who should receive recombinant human erythropoietin? 266 84

Child abuse, a clinical condition in young children who have received serious physical abuse, is a frequent cause of permanent injury or death. The first case is a 7-year-old boy suffering from abdominal distension and pain for 3 days. He was beaten by his mother as a result of inadequately learning his lessons. Sonogram and CT of the abdomen showed massive ascites and a pseudocyst of the pancreatic body about 3 x 3 cm in diameter. The second case is a 4-year-old girl who developed a semicomatose state after her father impulsively struck her with a chair. CT of the brain revealed subdural hematoma over the left fronto-temporal region and midline shift to the right. She expired 5 days later. The third case, a 2-year-old girl, suffered from headache, seizure, vomiting and general malaise. CT of the brain showed severe brain swelling over the right side and midline shift to the left. She expired 1 month later. Psychiatric factors are probably of prime importance in the pathogenesis of the disorder, but our knowledge of these factors is limited. Parents who inflict abuse on children do not necessarily have psychopathic or sociopathic personalities or come from borderline socioeconomic groups, although most published cases fall into one of these categories. It is clearly the responsibility of all physicians serving children to be aware of, to recognize, and to properly manage any child who has been the victim of abuse.
 ...
PMID:[Child abuse: report of three cases]. 270 Feb 79

Acute encephalopathy was associated with the appearance of antibodies to human T-lymphotropic virus (HTLV-III) in two patients. A third patient showed seroconversion for anti-HTLV-III, but the temporal association was not established so precisely. The illness was characterised by a prodromal period of up to 2 weeks, characterised by pyrexia, general malaise, and changes of mood. The encephalopathy culminated in epileptiform seizures in two of the patients. Electroencephalographic changes were compatible with viral encephalitis, and cerebrospinal-fluid pleocytosis was minimal. Neurological signs and symptoms resolved quickly in all patients, and no residual central-nervous-system sequelae were apparent.
 ...
PMID:Acute encephalopathy coincident with seroconversion for anti-HTLV-III. 286 90


1 2 3 4 5 6 7 Next >>