Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.
Epilepsy Res 1996 Nov
PMID:Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy. 895 19

The effects of topiramate in 15 patients with drug refractory epilepsy or Lennox-Gastaut syndrome were assessed in an open, add-on prospective study. After a follow-up of 14-21 months, six patients are still on topiramate (mean dosage 583 mg/day, range 400-800 mg/day), and nine have discontinued treatment because of adverse events (n = 6), inefficacy (n = 2) or poor compliance (n = 1). Nine patients (69%) continued to have > or = 50% reduction in seizure frequency during the last two months of treatment, and one has been seizure-free for the last 19 months. The most common adverse events were somnolence, weight loss, mental slowing, fatigue, ataxia and irritability. Most of these events were reversible, but withdrawal of treatment was required in six cases as a result of ataxia (two patients), somnolence, metabolic acidosis, irritability or psychotic symptoms (one patient each). It is concluded that topiramate is a valuable agent for long-term management of refractory epilepsy.
 ...
PMID:Efficacy and safety of topiramate in refractory epilepsy: a long-term prospective trial. 897 50

Medical issues in sport diving include illnesses that are caused by diving, and medical disorders that compromise safety. Cerebral air embolism and decompression sickness of the brain and spinal cord can result from diving. Sport divers may manifest a spectrum of symptoms from air embolism, which can range from unconsciousness to minimal symptoms, which include fatigue, personality change, poor concentration, irritability, and changes in vision. The physician must search for these minor symptoms in divers who are suspected of pulmonary barotrauma. Medical disorders of concern in diving include diseases of the lungs, the heart, the brain, and the endocrine system, particularly diabetes. Other factors involved in diving safety are exercise capacity and training. Clinical practice standards usually prohibit diving by individuals who have a seizure disorder that requires continuous medication. In the United States, we will not approve diving for individuals who have insulin-dependent diabetes or severe asthma. Some divers can return to diving after myocardial infarction or bypass surgery if they demonstrate good exercise tolerance and no ischemia on a graded exercise test, which simulates the physical activity needed for safe diving.
 ...
PMID:Medical aspects of sport diving. 914 89

The Neurotoxicity Scale was devised as a patient-based report scale to assess the adverse effects of antiepileptic drugs on cognitive function. In a previous report we reported the clinical validity of the scale, tested in a double-blind randomized study, using a benzodiazepine in normal volunteers. In the present study, the clinical sensitivity, construct validity and reliability of the scale was tested in patients with epilepsy. Patients (n = 189), selected from both participating centres, representative for the patients with chronic epilepsy were included in the study. Reliability was tested with Cronbachs alpha and yields an almost maximal score (.95). Clinical sensitivity was compared with the previous normal volunteer study and was evaluated as satisfactory. Construct validity showed a five-factor structure, explaining 66.5% of the variance, with 'fatigue and slowing' as the dominant factor. In line with the assumptions for this scale and with the results obtained in normal volunteers, the scale appears to be unsuitable for differential assessment of type or severity of drug-induced impairment. The most valid primary outcome measure is the overall score that renders a global ('all or nothing') evaluation indicating that a subject experiences cognitive impairment and associates this with the antiepileptic treatment. Other factors that may impair cognitive function, such as seizure frequency do not influence this score. The scale has therefore maximal applicability as a screening instrument in outpatient practice and in early (phase II, IIIa) drug trials.
Epilepsy Res 1997 Jun
PMID:The Neurotoxicity Scale--II. Results of a patient-based scale assessing neurotoxicity in patients with epilepsy. 923 50

Topiramate is a new antiepileptic drug which has recently become available in the United States and in a number of European countries. Pharmacological studies suggest that its mode of action is multifactorial and involves blockade of voltage-dependent sodium channels, potentiation of GABAergic transmission and inhibition of excitatory pathways through an action at AMPA receptor sites. Carbonic anhydrase inhibiting properties have also been demonstrated but they are considered not to be relevant to anticonvulsant activity. Topiramate is well absorbed from the gastrointestinal tract, peak plasma levels being usually attained in 2-3 hours. The drug is negligibly (9-17%) bound to plasma proteins and is eliminated partly by renal excretion in unchanged form and partly by oxidation and hydrolysis. In healthy volunteers, the half-life is about 20-30 hours, but elimination rate is accelerated in patients taking concomitant enzyme inducing drugs such as phenytoin, carbamazepine and barbiturates. Topiramate has no major effects on plasma levels of concurrent anticonvulsants, except for a rise in plasma phenytoin in occasional patients. In double-blind add-on trials in refractory partial epilepsy, a significant reduction in seizure frequency has been demonstrated in over 40% of topiramate-treated patients (vs about 10% of those treated with placebo), a response rate which compares favourably with that observed with other new antiepileptic drugs. Dosages found to be effective in add-on controlled trials range between 200 and 1000 mg day-1, although most patients are likely to benefit from receiving 400 mg day-1 or less. Preliminary data suggest that topiramate may be effective also in generalized epilepsies, but this needs to be confirmed in prospective studies. The most common adverse effects of topiramate are CNS-related and include dizziness, fatigue, visual disturbances, ataxia, mental slowing and impaired concentration. Paresthesias, anorexia, weight loss and increased risk of nephrolithiasis have been also reported. Many of these effects are related to dose and/or to rate of dose titration. Based on these data, topiramate appears to be a valuable new drug, whose main current indication is in the add-on management of refractory partial and secondarily generalized seizures. Studies on its potential-value as monotherapy are in progress.
 ...
PMID:A pharmacological and clinical review on topiramate, a new antiepileptic drug. 926 38

Gabapentin is a recently introduced antiepileptic drug for the treatment of partial seizures. Although studied extensively in adults, there have been few pediatric studies. It is a unique drug because it has no protein binding, is not metabolized, and is excreted through the kidneys. There are no significant drug interactions with other antiepileptic drugs nor do other antiepileptic drugs alter the pharmacokinetics of gabapentin. The drug is effective in partial seizures, although most studies have used the drug as add-on therapy. It is approved for use of partial seizures with or without secondary generalization in patients over the age of 12 years. The side effect profile of the drug is quite good. No significant idiosyncratic reactions have been reported. The most common side effects have included dizziness, fatigue, and headache. Rarely, children will have adverse behavioral effects, such as hyperactivity and agitated behavior. Usually these children have pre-existing behavioral disturbances. Although the spectrum of efficacy of gabapentin remains to be determined, it is likely to have a major beneficial impact on the treatment of childhood epilepsy.
 ...
PMID:Gabapentin for treatment of epilepsy in children. 932 92

Fifty patients with refractory partial seizures took part in a prospective, observational study of adjuvant gabapentin (GBP) in increasing doses. Thirty-three were started on 400 mg GBP daily with further weekly increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, not fully controlled on low dose GBP, followed the same regimen. All patients took the drug three times daily. Comparisons were made with seizure numbers during a 3-month baseline during which antiepileptic medication remained unchanged. Overall, 24 of the 50 patients documented a seizure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nine appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1:4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, headache and diplopia. On GBP doses exceeding 3600 mg daily, three patients developed flatulence and diarrhoea and two more had myoclonic jerks. Mean circulating GBP concentrations (mg/l) at each 1200 mg dose level were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg 13.2; 4800 mg 15.5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily, GBP concentrations continued to rise linearly at each dosage increment. Although limited, our results do not support the suggestion that GBP absorption is saturable. High dose GBP may be effective in controlling seizures in patients with refractory partial epilepsy.
Epilepsy Res 1998 Jan
PMID:High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients. 947 49

A 16 year old boy with epilepsy and learning difficulties is reported. At 3 years of age he was diagnosed with common acute lymphoblastic leukaemia, and received therapy according to the UK protocol, UKALL VIII. This included prophylactic CNS radiotherapy and chemotherapy. He did not develop CNS leukaemia, and complete remission was achieved. At age 7, he began to experience lethargy and learning difficulties, especially problems with hand-writing, concentration and memory. Furthermore, he began experiencing atypical absence seizures, which were provoked by concentration at times of tiredness. EEG showed bilateral non-specific abnormalities, with some epileptiform features. Over the following 9 years, several anti-epileptic drugs were prescribed. Although with the changes in therapy initial remissions have been achieved, the seizures have, each time, continued to relapse. At age 12, EEG was very abnormal, showing frequent generalized slow or sharp waves. At age 13, MRI revealed multiple discrete small high-intensity lesions in the subcortical white matter of both hemispheres. Problems with lethargy, concentration and memory persist and although multiple anti-epileptic drugs have been prescribed, seizures continue to occur almost daily.
 ...
PMID:Leukoencephalopathy after CNS prophylaxis for acute lymphoblastic leukaemia. 966 10

The cognitive complaints reported by children and their parents, as subjectively associated with antiepileptic drug (AED) treatment, were evaluated in seizure-free children before and after drug discontinuation. The aim of the design was to isolate the cognitive side effects of AEDs from other factors, such as the effect of seizures. Our inventory explored the following areas: "alertness," "concentration," "activation/ tiredness," "memory," "drowsiness," "depression," "aggressiveness," and "hyperactivity," using a 5-point Likert scaling procedure. One hundred two eligible patients were selected, each matched with a healthy control and assessed when still on antiepileptic medication. All children were seizure free for at least 1 year. The medication was then discontinued gradually over a 3-month period. Four months after the children were completely medication free, a second assessment was carried out, but only in the 83 children who remained seizure free and in their matched controls. The results of the reports made by the children themselves did not show differences with the matched controls, and only showed improvement after drug discontinuation for complaints about "tiredness." Parents of the children with epilepsy reported significant improvement in all areas related to "alertness and activation" after discontinuation of the drugs. The finding that only a limited number of children have cognitive complaints, both when still on AEDs and after discontinuation, may be in line with the reports that the major factor contributing to quality of life is whether patients are seizure free or still have seizures. All patients in this study were seizure free for a period >1 year, which may have caused the favorable pattern of response in our patient group.
 ...
PMID:Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation. 977 27

Constrained arthroplasty is occasionally needed to salvage a destroyed glenohumeral joint when the rotator cuff is nonfunctioning and when an unconstrained prosthesis will not suffice. There is a high failure rate because of the severe forces between such a device and the contiguous bone. Accordingly, it is essential to know the limitations of constrained arthroplasty and when it should be avoided. For example, when the bone of the glenoid vault is highly demineralized or deficient or if there is a history of seizure disorder or alcoholism, use of such a device is contraindicated. Postoperatively, excessive force and extremes of motion should also be avoided during the rehabilitation program to avoid bone fracture or dislocation of the prosthesis. Various complications have been observed with constrained arthroplasty, including dislocation, bone fracture, pullout of the glenoid, infection, radial nerve injury after extrusion of bone cement through the humeral cortex when the cement has been pressurized, and screw breakage in a relative small number of cases after metal fatigue and loosening of the glenoid component. When the glenoid component has pulled away from the glenoid vault, it may be necessary to remove this component; the humeral head may be fitted with a bipolar 40- to 44-mm acetabular component, thereby allowing at least preservation, if not the active function of the shoulder contour.
 ...
PMID:Constrained arthroplasty: its use and misuse. 1014 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>