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

The Octopus 2000 computerized perimeter (Interzeag, Schlieren, Switzerland) is combined with an infrared videopupillograph (Demel, Haan, FRG) which at the same time records the direct pupil light response and controls fixation. Digital processing of the pupil video image is performed at a rate of 25 cps. A transient oscilloscope display of the pupil surface after each light stimulus covers the subsequent 1000 ms, so that either pupillary light reflexes or the lack of a response can immediately be identified. An additional continuous penwriter printout shows light stimuli, pupil responses and the subject's responses. Thus, potential discrepancies between the pupil response and the subject's response are clearly revealed. The examination conditions slightly deviate from the standard ones used with the Octopus. Stimulus size is analogous to the target Goldmann/V, the stimulus duration 100 ms and the adaptive illumination 1 cd/m2. Pupil fatigue considerably exceeds visual fatigue. Therefore standard Octopus perimetric programs are inconvenient for pupilloperimetric purposes. A Sargon-based pupilloperimetric program determines pupillomotor increment thresholds at 12 stimulus locations throughout the visual field (20 degrees nasal, 0 degrees, 20 degrees and 40 degrees temporal/15 degrees above the 0 degrees meridian, 0 degrees meridian and 15 degrees below the 0 degrees meridian) while applying the normal Octopus strategy of threshold calculation. Instead of the patient's subjective responses, the examiner's assessment of pupil responses provides the basis for threshold determination by the Octopus program. The subjects are unaware of the mode of examination. Their rating of "seen" or "not seen" ist displayed together with the pupil responses, thus providing a hard copy as proof of malingering or of appropriate cooperation.
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PMID:[Pupillographic perimetry using the "Octopus"]. 262

We studied eight women who had complex partial seizures and anovulatory cycles or inadequate luteal phases. Progesterone suppositories were given during the premenstrual phase or entire second half of the cycle in doses of 50 to 400 mg q12h. Antiseizure medication levels were kept in the therapeutic range. Average monthly seizure frequency declined by 68% (p less than 0.05, Wilcoxon matched-pairs test) in a 3-month treatment period compared with the 3 months prior to therapy, and six of the eight women had fewer seizures. None experienced more seizures or disruption of menses. Transient tiredness and depression were noted in some when progesterone dosage was raised above minimally effective levels. These symptoms cleared within 48 hours of lowering the dosage. The value of intermittent natural progesterone therapy as a safe, well-tolerated, and effective adjunct to antiseizure therapy should be assessed further.
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PMID:Intermittent progesterone therapy and frequency of complex partial seizures in women with menstrual disorders. 378 77

We carried out an open study of the effects of large doses (12 to 16 gm per day) of oral choline on medically intractable human complex partial seizures (CPS). Marked increases of plasma choline concentration (75 to 300%) in three subjects were associated with (1) shorter duration of CPS, (2) less postseizure fatigue, and (3) slight increase of seizure frequency. Both the patients and their families considered the patients much improved. No differences in any of these evaluations were noted in a fourth subject who had less of an increase (21%) of plasma choline content. The results suggest that oral choline therapy may be a useful adjunct in the treatment of intractable CPS. A blinded prospective study will be necessary to assess this possibility.
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PMID:Effects of oral choline on human complex partial seizures. 677 20

The present examination shows the action of the acoustic reflex on stimulation with a pure tone of 500 cps which lies 10 dB above the reflex threshold by impedance measurement. The duration of stimulation lasts 5 min. The test results of persons with normal hearing, persons with cochlear and retrocochlear lesions were measured according to the amount, the duration, the beginning, and the speed of reflex decay. The preliminary results permit the following conclusions: Persons with noise-induced hearing loss show no reflex decay for the entire duration of stimulation. Persons with normal hearing show a reflex decay after 2 min. After another 135 sec a constant reflex amplitude is attained. Subjects with cochlear lesions which are not caused by noise show similar reflex behavior. The amount of decay is larger, and the decay begins earlier. Persons with retrocochlear lesions show heterogeneous results, but the average amplitudinal decay is rapid and exceeds 50 per cent. The underlying mechanisms are discussed. In our opinion muscle fatigue plays an important role, which is absent in noise-induced hearing loss due to a permanent muscle training caused by the chronic noise exposure. The main result for audiology lies in the possibility to distinguish clearly between noise-induced hearing loss and other forms of cochlear lesions.
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PMID:[Behavior of the stapedius reflex in long-term acoustic stimulation]. 715 3

Tiagabine is a new antiepileptic drug which acts by a novel mechanism, inhibiting the reuptake of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into neurons and glia. A double-blind, placebo-controlled, crossover trial was undertaken, based upon a response-dependent design. Ninety-four patients with complex partial seizures with or without secondary generalised tonic-clonic seizures were recruited into an open screening phase and tiagabine was added to their existing drug therapy in doses titrated to reduce seizure frequency by > or = 25% or to the limit of tolerance. Forty-six responders were subsequently randomised to a double-blind crossover trial in which tiagabine was compared with placebo. Forty-two patients completed the trial. A significant reduction in the frequency of complex partial and secondary generalised tonic clonic seizures was seen. Twenty-six percent had a reduction of > or = 50% in the frequency of their complex partial seizures, and of the 27 patients who also had secondary generalised tonic clonic seizures, 63% experienced a reduction of > or = 50%. No interactions with baseline antiepileptic drugs were detected and no serious adverse reactions occurred. The commonest adverse events were tiredness, dizziness and headache. We conclude that tiagabine has promising antiepileptic effects. Further trials are underway.
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PMID:Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial. 764 74

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32

A 53-year-old woman began taking felbamate for uncontrolled complex partial seizures. Four months later, she developed fatigue and ecchymotic skin lesions. Laboratory studies revealed very severe aplastic anemia. There have been an additional nine reported cases of aplastic anemia in the setting of felbamate treatment. The association between felbamate and aplastic anemia has resulted in a joint recommendation by the US Food and Drug Administration and the manufacturer of felbamate, Carter-Wallace, Inc., for the immediate withdrawal of patients from treatment with felbamate.
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PMID:Aplastic anemia in a patient receiving felbamate for complex partial seizures. 789 96

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.
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PMID:Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. 832 80

ASTA Medica is developing retigabine, a carbamic acid ethyl ester and a selective potassium channel opener, for the treatment of complex partial seizures. Phase II trials have commenced [249117], and a multicenter placebo-controlled dosage-finding study has begun in Europe and Australia [392702]. Retigabine is also undergoing phase II testing in Germany, Switzerland, Russia and the US for the potential treatment of epilepsy [323383]. Phase II trials have shown >50% reduction in seizure frequency in 12 of 35 patients with refractory epilepsy [373379]. Phase I clinical trials for epilepsy were successfully completed in Germany in 1995 [180371]. Single and multiple dose trials demonstrated the tolerability and favorable pharmacokinetic behavior of the compound [264306]. The compound showed good compatibility and exhibits an antisense anticonvulsive effect in various preclinical epilepsy models [250565,299344]. Side effects of mild to moderate tiredness, fatigue and nausea were observed [276123]. The spectrum of activity of retigabine resembles that of valproate, but its potency is greater and toxicity is reduced [373379]. The mechanism of action of retigabine is probably multifactorial. Research has shown that retigabine acts as a selective K+ channel opener in neuronal cells and this can be expected to contribute to its anticonvulsant effect [273670]. In addition it demonstrates potentiation of GABA transmission and possibly also weak modulation of sodium and calcium channels [299344]. Retigabine also has neuroprotective activity with potential for the treatment of stroke and neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease and multiple sclerosis [249381]. In February 2000, Lehman Brothers predicted product launch could be as early as 2002 for epilepsy in the US [357788]. In February 1999, Lehman Brothers predicted that the first major launch date of the drug would be 2003, and the year of peak sales to be 2011 [319225].
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PMID:Retigabine (ASTA Medica). 1603 7

Topiramate is an antiepileptic drug with a beneficial clinical effect on various seizure types. Topiramate does not seem to be associated with serious adverse effects and is also well tolerated in pediatric patients. Only few cases of hypohidrosis have been described. This report presents one young patient with complex partial seizures who was medicated with topiramate when she developed fatigue, headache, intermittent hyperthermia, inability to produce sweat secretion, and dryness of the skin. Reduced sweat response was determined using the Wescor Macroduct collection procedure. Topiramate was discontinued, and within 3 weeks a repeat sweat test was completely normal. At that time, clinical signs had also disappeared. Hypohidrosis is an uncommon and reversible side effect reported in association with topiramate therapy. It is rare in patients on monotherapy. Although a definite causal relationship still needs to be established, this side effect might be attributed to an autonomic dysfunction by inhibition of isoenzymes of carbonic anhydrase localized in human eccrine sweat glands.
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PMID:Hypohidrosis during topiramate treatment: a rare and reversible side effect. 1713 20


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