The effect of acupuncture in chronic intractable epilepsy.
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We examined the effect of acupuncture on epileptic seizures in humans in a controlled clinical setting. Treatment was administered by two Chinese professors of acupuncture. Effect was measured by change in seizure frequency. Twenty-nine patients with chronic intractable epilepsy completed the study. They were randomized in two groups; 15 were given classical acupuncture and 14 were given sham acupuncture. There was a reduction in seizure frequency in both groups, which did not reach a level of statistical significance. There was also an increase in the number of seizure-free weeks in both groups, which reached a level of significance in the sham group. Thus, we have not been able to prove a beneficial effect of acupuncture in chronic intractable epilepsy. (+info)
The influence of age on propofol pharmacodynamics.
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BACKGROUND: The authors studied the influence of age on the pharmacodynamics of propofol, including characterization of the relation between plasma concentration and the time course of drug effect. METHODS: The authors evaluated healthy volunteers aged 25-81 yr. A bolus dose (2 mg/kg or 1 mg/kg in persons older than 65 yr) and an infusion (25, 50, 100, or 200 microg x kg(-1) x min(-1)) of the older or the new (containing EDTA) formulation of propofol were given on each of two different study days. The propofol concentration was determined in frequent arterial samples. The electroencephalogram (EEG) was used to measure drug effect. A statistical technique called semilinear canonical correlation was used to select components of the EEG power spectrum that correlated optimally with the effect-site concentration. The effect-site concentration was related to drug effect with a biphasic pharmacodynamic model. The plasma effect-site equilibration rate constant was estimated parametrically. Estimates of this rate constant were validated by comparing the predicted time of peak effect with the time of peak EEG effect. The probability of being asleep, as a function of age, was determined from steady state concentrations after 60 min of propofol infusion. RESULTS: Twenty-four volunteers completed the study. Three parameters of the biphasic pharmacodynamic model were correlated linearly with age. The plasma effect-site equilibration rate constant was 0.456 min(-1). The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6 min (range, 1-2.4 min). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C50 values for loss of consciousness of 2.35, 1.8, and 1.25 microg/ml in volunteers who were 25, 50, and 75 yr old, respectively. CONCLUSIONS: Semilinear canonical correlation defined a new measure of propofol effect on the EEG, the canonical univariate parameter for propofol. Using this parameter, propofol plasma effect-site equilibration is faster than previously reported. This fast onset was confirmed by inspection of the EEG data. Elderly patients are more sensitive to the hypnotic and EEG effects of propofol than are younger persons. (+info)
Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients.
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BACKGROUND: Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. METHODS: A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. RESULTS: The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients. CONCLUSIONS: The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly. (+info)
Brain O2 consumption and glutamate release during hypoglycemic coma in piglets are temperature sensitive.
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Hypoglycemic injury in the mature brain is mediated by excitotoxicity, which is worsened by disordered cellular energy metabolism. The role of excitotoxicity in relation to brain energy metabolism during hypoglycemia has not been studied in the immature brain. Brain oxygen consumption (CMRO2) increases during hypoglycemia in piglets, whereas CMRO2 decreases in adult pig models. We tested the hypothesis that increased CMRO2 during hypoglycemic coma is temperature dependent and coincides with increased excitatory amino acids (EAA). We measured cerebral blood flow (CBF), CMRO2, and cortical microdiaysate EAA in pentobarbital-anesthetized piglets during hypoglycemic coma and during 2 h of recovery and in normoglycemic controls. In warmed animals brain temperature was kept normothermic (38.5 degrees C). In unwarmed animals brain temperature was allowed to fall (37.6 degrees C). During hypoglycemia CBF increased similarly in warmed animals and unwarmed animals; CMRO2 increased in warmed animals but not unwarmed animals. Glutamate increased during coma and increased more in warmed animals than unwarmed animals but normalized quickly during recovery. EEG recovered earlier in unwarmed animals. We conclude that during a hypoglycemic coma in the immature brain, CMRO2 and glutamate are increased in a temperature-dependent manner. (+info)
Effect of propofol on the electrocorticogram in epileptic patients undergoing cortical resection.
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We have compared the effect of clinical doses of propofol with thiopental on epileptiform activity in the electrocorticograms (ECoG) of 20 epileptic patients undergoing temporal lobe resection. After baseline ECoG had been obtained, with inspired concentrations of 0.5-1% isoflurane and 70% nitrous oxide to provide background anaesthesia, subjects were allocated randomly to receive boluses of either thiopental 25 mg or propofol 20 mg i.v. every 30 s to a maximum of 5 mg kg-1 or until burst suppression was seen. The ECoG was recorded throughout administration and for 10 min thereafter. After return of baseline ECoG tracings, the alternate agent was administered. The amount of epileptiform activity was recorded on an ordinal rating scale, an increase being indicated by either a rise of at least one category on the scale or discharges occurring at a minimum of one new site. Activation occurred more frequently with thiopental but the difference was not significant. This study suggests that propofol has no greater proconvulsive effect than thiopental, a drug commonly used in managing status epilepticus. (+info)
Prediction of movement at laryngeal mask airway insertion: comparison of auditory evoked potential index, bispectral index, spectral edge frequency and median frequency.
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We have studied 46 patients to compare the efficacy of the auditory evoked potential (AEP) index, bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) in predicting movement in response to insertion of the laryngeal mask airway (LMA). Anaesthesia was induced with target-controlled infusions of propofol and alfentanil. After loss of eyelash reflex and adequate jaw relaxation, the LMA was inserted without the assistance of a laryngoscope or neuromuscular blocker. Patients who showed any visible spontaneous muscle movement within 1 min of LMA insertion were defined as movers. Values in movers and non-movers at 30 s before LMA insertion were analysed. Only AEP index discriminated between movers and non-movers with a prediction probability of 0.872. BIS, SEF and MF could not predict movement at LMA insertion. AEP index was the most reliable predictor of movement in response to LMA insertion. (+info)
Interleukin-1beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures.
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Using immunocytochemistry and ELISA, we investigated the production of interleukin (IL)-1beta in the rat hippocampus after focal application of kainic acid inducing electroencephalographic (EEG) seizures and CA3 neuronal cell loss. Next, we studied whether EEG seizures per se induced IL-1beta and microglia changes in the hippocampus using bicuculline as a nonexcitotoxic convulsant agent. Finally, to address the functional role of this cytokine, we measured the effect of human recombinant (hr)IL-1beta on seizure activity as one marker of the response to kainate. Three and 24 hr after unilateral intrahippocampal application of 0.19 nmol of kainate, IL-1beta immunoreactivity was enhanced in glia in the injected and the contralateral hippocampi. At 24 hr, IL-1beta concentration increased by 16-fold (p < 0.01) in the injected hippocampus. Reactive microglia was enhanced with a pattern similar to IL-1beta immunoreactivity. Intrahippocampal application of 0.77 nmol of bicuculline methiodide, which induces EEG seizures but not cell loss, enhanced IL-1beta immunoreactivity and microglia, although to a less extent and for a shorter time compared with kainate. One nanogram of (hr)IL-1beta intrahippocampally injected 10 min before kainate enhanced by 226% the time spent in seizures (p < 0.01). This effect was blocked by coinjection of 1 microgram (hr)IL-1beta receptor antagonist or 0.1 ng of 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate, selective antagonists of IL-1beta and NMDA receptors, respectively. Thus, convulsant and/or excitotoxic stimuli increase the production of IL-1beta in microglia-like cells in the hippocampus. In addition, exogenous application of IL-1beta prolongs kainate-induced hippocampal EEG seizures by enhancing glutamatergic neurotransmission. (+info)
Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin.
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Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 microg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin. (+info)