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PubMed2000

Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot-spot is not elevated above the genome average rate.

An increasing number of human diseases and syndromes are being found to result from micro-duplications or microdeletions arising from meiotic recombination between homologous repeats on the same chromosome. The first microduplication syndrome delineated, Charcot-Marie-Tooth disease type 1A (CMT1A), results from unequal crossing over between two >98% identical 24 kb repeats (CMT1A-REPs) on chromosome 17. In addition to its medical significance, the CMT1A region has features that make it a unique resource for detailed analysis of human unequal recombination. Previous studies of CMT1A patients showed that the majority of unequal crossovers occurred within a small region (<1 kb) of the REPs suggesting the presence of a recombination hot-spot. We directly measured the frequency of unequal recombination in the hot-spot region using sperm from four normal individuals. Surprisingly, unequal recombination between the REPs occurs at a rate no greater than the average rate for the male genome (approximately 1 cM/Mb) and is the same as that expected for equally aligned REPs. This conclusion extends to humans the findings in yeast that recombination between repeated sequences far apart on the same chromosome may occur at similar frequencies to allelic recombination. Finally, the CMT1A hot-spot stands in sharp contrast to the human MS32 mini-satellite-associated hot-spot that exhibits highly enhanced recombination initiation in addition to positional specificity. One possibility is that the CMT1A hot-spot may consist of a region with genome average recombination potential embedded within a recombination cold-spot.

Adult↗
PubMed2003

Temporal summation governs part of the minimum alveolar concentration of isoflurane anesthesia.

BACKGROUND: General anesthesia may delay the onset of movement in response to noxious stimulation. The authors hypothesized that the production of immobility could involve depression of time-related processes involved in the generation of movement. METHODS: The delays (latencies) between onset of tail clamp (n = 16) or 50-Hz continuous electrical stimulation (n = 8) and movement were measured in rats equilibrated at 0.1-0.2% increasing steps of isoflurane. In other rats (n = 8), the isoflurane concentrations just permitting and preventing movement (crossover concentrations) in response to trains of 0.5-ms 50-V square-wave pulses of interstimulus intervals of 10, 3, 1, 0.3, or 0.1 s during the step increases were measured. These measures were again made during administration of intravenous MK801, an N-methyl-D-aspartate receptor antagonist that can block temporal summation (n = 6). Temporal summation refers to the cumulative effect of repeated stimuli. Crossover concentrations to 10- and 0.1-s interstimulus interval pulses ranging in voltage from 0.25-50 V were also measured (n = 4). RESULTS: The increase in concentrations from 0.6 to nearly 1.0 minimum alveolar concentration progressively increased latency from less than 1 s to 58 s. Shortening the interstimulus interval (50 V) pulses from 10 to 0.1 s progressively increased crossover concentrations from 0.6 to 1.0 minimum alveolar concentration. In contrast, during MK801 administration shortening interstimulus intervals did not change crossover concentrations, producing a flat response to change in the interstimulus interval. Increasing the voltage of interstimulus interval pulses increased the crossover concentrations but did not change the response to change in interstimulus intervals for pulses greater than 1 V. CONCLUSIONS: Increasing the duration or frequency (interstimulus interval) of stimulation increases the concentration of isoflurane required to suppress movement by a 0.4 minimum alveolar concentration MK801 blocks this effect, a finding consistent with temporal summation (which requires intact N-methyl-D-aspartate receptor activity) at concentrations of up to 1 minimum alveolar concentration isoflurane.

Anesthetics, Inhalation↗
PubMed2005

Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics.

BACKGROUND: Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established. AIM: To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine. METHODS: Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double-blind, four-way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) "beta" frequency activity were also assessed. RESULTS: Fluvoxamine significantly reduced apparent oral clearance of caffeine (105 vs. 9.1 mL min(-1), P < 0.01; mean difference: 95.7 mL min(-1), 95% CI: 54.9-135.6), and prolonged its elimination half-life (4.9 vs. 56 h, P < 0.01; mean difference: 51 h, 95% CI: 26-76). Caffeine produced CNS-stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine. CONCLUSIONS: Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine-treated individuals.

Area Under Curve↗
PubMed1986

Effects of 50 Hz electric currents on mood and verbal reasoning skills.

Seventy-six male volunteers were studied in a crossover trial to assess the impact on the central system of electric currents such as might be induced by exposure to an intense power frequency electric field. Currents totalling 500 microamperes (50 Hz) were passed through electrodes attached to the head, upper arms, and feet, simulating exposure of and average man to a vertical electric field of about 36 kV/m. Exposure was continuous for a single day (5.5 hours) and the experiment was based on a double blind, counterbalanced, within subject design. A series of psychological tests examining self reports of both stress and arousal (mood checklist) and performance tests of memory, attention, and verbal skills were administered. Although the double blind conditions were compromised to some extent by reported sensations at electrode sites, the duration of these sensations was small in relation to the overall exposure or sham exposure time and did not interact with the effects apparently associated with exposure that were found. No significant difference between the exposed and sham-exposed groups was found on the first day, but on the second day the sham exposed group felt more aroused at the end of the day and their response times had improved more on the complex problems of a syntactic reasoning test. No exposure effects were apparent in self reports of stress or in performance in a semantic reasoning test, although both showed some influence of sensations. Interpretation of the exposure effects is complicated by their apparent restriction of the second test day, which may indicate some type of state dependent transfer phenomenon.

Adolescent↗
PubMed1994

Morning increase in ambulatory ischemia in patients with stable coronary artery disease. Importance of physical activity and increased cardiac demand.

BACKGROUND: The morning increase in asymptomatic ambulatory ischemia may be due to heightened coronary tone, increased physical activity, or both. If ambulatory ischemia is primarily due to physical activity, then alterations in the schedule of physical activity should be reflected in a corresponding alteration in the occurrence of ischemia. This study was designed to examine the relation between activity patterns and the frequency of ambulatory ischemic episodes and the effect of nadolol on these relations. METHODS AND RESULTS: A double-blind, randomized, placebo-controlled, crossover trial of nadolol versus placebo was performed in 20 patients with stable coronary artery disease. At the end of each 2-week treatment phase, patients were hospitalized for 48 hours. In the hospital, there was a regular activity day (awaken and assume normal activities at 8:00 AM) and a delayed activity day (awaken at 8:00 AM, arise at 10:00 AM, and begin normal activity at noon). Ambulatory ECG monitoring was performed throughout the hospitalization. On the regular activity day, there was a morning increase in heart rate and in the number of ischemic episodes during therapy with placebo that began at 8:00 AM. In contrast, on the delayed activity day, there was a 4-hour phase shift of the increases in heart rate and the increase in ischemic episodes (ie, at noon) corresponding to the onset of physical activities. Therapy with nadolol caused a 50% reduction in the total number of ischemic episodes (129 versus 65, placebo versus nadolol; P < .02). During nadolol therapy, there was no discernible circadian peak in the number of ischemic episodes on either activity day. During placebo treatment, 87% of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. Although nadolol caused a significant reduction in the total number of episodes preceded by a heart rate increase compared with placebo (99 versus 38 episodes, P < .04), this therapy was associated with a significant increase in the number of episodes not associated with a heart rate increase (15 versus 21 episodes, P < .002). CONCLUSIONS: The morning increase in ambulatory ischemic episodes is due to physical activity patterns. The majority of ischemic episodes are preceded by a heart rate increase, and it is these episodes that are primarily responsible for the morning increase in ischemia. Therapy with nadolol caused a reduction in the total number of ischemic episodes solely by reducing those episodes preceded by a heart rate increase. In contrast, nadolol caused a significant increase in the number of ischemic episodes not associated with a heart rate increase, perhaps in part because it potentiated coronary vasoconstriction.

Aged↗
PubMed2004

Closed suctioning system reduces cross-contamination between bronchial system and gastric juices.

In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.

Aged↗
PubMed1975

Effects of noise bands on contralateral pure tone adaptation.

The purpose of this study was to investigate the changes in threshold tone decay which result from contralaterally presented stimuli at an intensity less than interaural crossover. Five tone decay tests were administered at both 1,000 Hz and 2,000 Hz to 25 normal hearing adults. At each test frequency five contralateral conditions (no competing noise, white noise, narrow band noise centered at the test frequency, narrow band noise centered below the test frequency, and narrow band noise centered above the test frequency), were presented at 40 db above detection threshold to the nontest ear. Results showed a significant shift in tone decay scores when the conditions of white noise and narrow band noise centered around the test frequency were compared to the condition of no competing noise. A shift was seen at both frequencies but that occuring at 2,000 Hz was significantly greater than the shift at 1,000 Hz. No significant increase in tone decay was found for contralateral noise bands above or below the test frequencies.

Adolescent↗
PubMed1994

[Stress factors in acute myocardial infarct: the role of physical exertion and unusual life events].

OBJECTIVE: It is controversial whether the onset of myocardial infarction is a "random" event or whether there are triggering factors of the disease. Previous reports on possible triggers were based on case studies or inadequately controlled studies. The TRIMM study (Triggers and Mechanisms of Myocardial Infarction) was designed to determine the influence of physical activity and other external factors on the acute risk of myocardial infarction. METHODS: At Klinikum Steglitz, Berlin, all consecutive patients with myocardial infarction were included. In the Augsburg area, all patients with myocardial infarction in a prospectively defined cohort (n = 330,000) were registered by monitoring 26 hospitals. Information on the circumstances and possible triggers of the disease was obtained by standardized interviews. The control group was matched for age, sex, precinct, and time of a control event. The statistical analysis included a case-control comparison of patients with control subjects and a case-crossover comparison comparing the average exposure to a possible trigger with the time of the last exposure prior to the onset of disease. RESULTS: From January 1989 to December 1991, 1194 patients (74% men, 61 +/- 9 years) were enrolled 13 +/- 6 days after myocardial infarction. During the initial three hours after awakening, the occurrence of myocardial infarction was almost threefold compared to other times of day. A multivariate analysis yielded a twofold risk of myocardial infarction during physical exertion, statistically independently of time of day. 7.1% of patients had engaged in exertional physical activity at onset of the event, as opposed to 3.9% of control subjects. The case-crossover analysis demonstrated a relative risk of 2.1 (1.6-3.1) of exertional physical activity within 1 hour prior to myocardial infarction. Patients whose average frequency of physical exertion was < 4 versus > or = to 4 times per week had relative risks of 6.9 versus 1.3 (p < 0.01). Unusual life events within 24 hours and 24 hours to 4 weeks prior to the event occurred with similar frequencies and control subjects. CONCLUSIONS: Physical exertion appears to increase the acute risk of myocardial infarction in patients with coronary heart disease, particularly in untrained individuals. Unusual life events, however, are of less importance for the acute risk of disease. These findings are important for further investigation of triggering mechanisms of myocardial infarction and for improving preventive strategies.

Adult↗
PubMed1992

Frequency-importance functions for words in high- and low-context sentences.

The relative importance and absolute contributions of various spectral regions to speech intelligibility under conditions of either neutral or predictable sentential context were examined. Specifically, the frequency-importance functions for a set of monosyllabic words embedded in a highly predictive sentence context versus a sentence with little predictive information were developed using Articulation Index (AI) methods. Forty-two young normal-hearing adults heard sentences presented at signal-to-noise ratios from -8 to +14 dB in a noise shaped to conform to the peak spectrum of the speech. Results indicated only slight differences in 1/3-octave importance functions due to differences in semantic context, although the crossovers differed by a constant 180 Hz. Methodological and theoretical aspects of parameter estimation in the AI model are discussed. The results suggest that semantic context, as defined by these conditions, may alter frequency-importance relationships in addition to the dynamic range over which intelligibility rises.

Adolescent↗
PubMed2000

A case-crossover analysis of a case-control study of alcohol consumption and coronary events: the effects of exposure definition and the use of control data.

BACKGROUND: Case-crossover studies can be used to assess the effects of transient exposures in acute events by comparing cases' exposures at the time of the event against their usual exposure. Cases from a case-control study can also be analysed by this method if appropriate information is obtained. METHODS: We apply the case-crossover method to data collected in a case-control study of acute coronary events, to estimate the risk of alcohol consumption in the 24 h before a coronary event. Two questions, concerning the usual frequency of consuming alcohol and how much was consumed, were used in the analysis. The sensitivity of effect estimates to the two questions and to different ways of eliciting probabilities from them, are examined. The cases and controls were both analysed in the same way, assigning controls a 'pseudo-event' time at random. It is suggested that controls may provide a benchmark to establish whether bias exists in the case-series analysis. RESULTS: We find that the case-crossover analysis is sensitive to how exposure probabilities are assigned. Adopting a Poisson model for exposures leads to inflated risk estimates. The bias is removed if the control series is used to adjust estimates. There appears to be a small protective effect from alcohol consumption. CONCLUSION: Case-crossover designs have considerable potential, but reliable information on usual exposure limits their applicability. More research is required on how best to elicit exposure probabilities.

Alcohol Drinking↗
PubMed2003

Changes in dynamic crossover with temperature and pressure in glass-forming diethyl phthalate.

Dielectric relaxation measurements have been used to study the crossover in dynamics with temperature and pressure, onset of breakdown of the Debye-Stokes-Einstein law, and the relation between the alpha and the beta relaxations in diethyl phthalate. The measurements made over 10 decades in frequency and a broad range of temperature and pressure enable the dc conductivity and the alpha- and the beta-relaxations to be studied altogether. The isobaric data show that the alpha-relaxation time tau(alpha) has temperature dependence that crosses over from one Vogel-Fulcher-Tammann-Hesse form to another at T(B) approximately 227 K and tau(alpha) approximately 10(-2) s. The dc conductivity sigma exhibits similar crossover at the same T(B). At temperatures above T(B), tau(alpha) and sigma have the same temperature dependence, but below T(B) they become different and the Debye-Stokes-Einstein law breaks down. The breadth of the alpha relaxation is nearly constant for T T(B). The time dependence of tau(beta) is Arrhenius, which when extrapolated to higher temperatures intersects tau(alpha) at T(beta) nearly coincident with T(B). Isothermal measurements at various applied pressures when compared with isobaric data show that the shape of the alpha-relaxation depends only on tau(alpha), and not on the T and P combinations. At a constant temperature, while tau(alpha) increases rapidly with pressure, the beta-relaxation time tau(beta) is insensitive to applied pressure. This behavior is exactly the same as found in 1,1(')-bis (p-methoxyphenyl) cyclohexane. The findings are discussed in the framework of the coupling model.

Journal Article↗
PubMed2002

Genetic proof of unequal meiotic crossovers in reciprocal deletion and duplication of 17p11.2.

A number of common contiguous gene syndromes have been shown to result from nonallelic homologous recombination (NAHR) within region-specific low-copy repeats (LCRs). The reciprocal duplications are predicted to occur at the same frequency; however, probably because of ascertainment bias and milder phenotypes, reciprocal events have been identified in only a few cases to date. We previously described seven patients with dup(17)(p11.2p11.2), the reciprocal of the Smith-Magenis syndrome (SMS) deletion, del(17)(p11.2p11.2). In >90% of patients with SMS, identical approximately 3.7-Mb deletions in 17p11.2 have been identified. These deletions are flanked by large (approximately 200 kb), highly homologous, directly oriented LCRs (i.e., proximal and distal SMS repeats [SMS-REPs]). The third (middle) SMS-REP is inverted with respect to them and maps inside the commonly deleted genomic region. To investigate the parental origin and to determine whether the common deletion and duplication arise by unequal crossovers mediated through NAHR between the proximal and distal SMS-REPs, we analyzed the haplotypes of 14 families with SMS and six families with dup(17)(p11.2p11.2), using microsatellite markers directly flanking the SMS common deletion breakpoints. Our data indicate that reciprocal deletion and duplication of 17p11.2 result from unequal meiotic crossovers. These rearrangements occur via both interchromosomal and intrachromosomal exchange events between the proximal and distal SMS-REPs, and there appears to be no parental-origin bias associated with common SMS deletions and the reciprocal duplications.

Abnormalities, Multiple↗
PubMed1996

[Clinical consequences of intranasal insulin therapy in insulin-dependent diabetes mellitus].

Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control, assessed by haemoglobin A1c concentrations, deteriorated after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosal physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.

Administration, Intranasal↗
PubMed1997

Comparison of the effects of two weeks' intervention with different meal frequencies on glucose metabolism, insulin sensitivity and lipid levels in non-insulin-dependent diabetic patients.

AIMS: To compare the effects of 2 weeks on different meal frequencies on glucose metabolism, lipid levels and 24-hour blood pressure in non-insulin-dependent diabetic subjects. METHODS: Ten non-insulin-dependent diabetic outpatients from Aarhus City participated in a crossover study design. None were treated with insulin. The patients were randomly allocated to two isoenergetic diets either taken as three or eight meals per day for 2 weeks each. At the end of each period, the diurnal blood pressure and the responses to a test meal were measured. Furthermore, a hyperinsulinemic, euglycemic clamp was placed. RESULTS: Both the insulin sensitivity and 24-hour ambulatory blood pressure were similar as were the responses of glucose, insulin and free fatty acids to a carbohydrate-rich test meal at the end of the two diet periods. The HDL-cholesterol level was lowest in response to the 8-meal diet (p = 0.02). CONCLUSION: Increasing meal frequencies in a 2-week treatment period with weight-maintaining diets on an outpatient basis subdued the HDL-cholesterol levels but apparently had no impact on glucose metabolism or diurnal blood pressure in NIDDM subjects. These results give no indications of long-term beneficial effects of increasing the meal frequency in NIDDM patients.

Blood Glucose↗
PubMed1983

Nifedipine as a therapeutic modality for Raynaud's phenomenon.

Eight patients with Raynaud's phenomenon were entered into a double-blind crossover study of nifedipine versus placebo, with 7 patients undergoing finger plethysmography before and after sublingual nifedipine administration. While receiving nifedipine, all patients reported decreased frequency and severity of attacks, and 4 of 5 had digital ulcer healing. Total finger blood flow increased 5 of 6 patients after treatment with sublingual nifedipine. This preliminary study indicates that nifedipine may be a useful agent for treatment of digital vasospasm.

Adult↗
PubMed1999

Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers.

RATIONALE: CNS-active drugs produce specific electroencephalographic changes and the concentration-effect relationship of antipsychotics may be elucidated by adopting electroencephalography (EEG) as an effect measurement tool. OBJECTIVE: The purpose of the present study was to determine the concentration-effect relationship of risperidone by assessing the EEG effect after oral administrations of single dose risperidone in healthy young males. METHODS: Nine healthy male volunteers received a 1 mg single oral dose of risperidone according to a placebo controlled crossover design. Plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone were measured by radioimmunoassay. Quantitative EEG parameters were obtained for each of four frequency bands through spectral EEG analysis. The difference in the absolute power in the delta frequency band for the F3 lead between risperidone and placebo was used as a drug effect parameter. For pharmacokinetic-pharmacodynamic modeling, the hypothetical effect compartment kinetically linked to plasma by a first-order process was postulated. All curve fittings were done with the non-linear curve-fitting program NONLIN. RESULTS: Our results showed that absolute powers in delta and theta frequency bands were higher for risperidone administration than for placebo at all EEG leads, and the maximum effects were detected at about 3 h after administration of the drug. The hysteresis loop was observed in the plot of plasma concentration of risperidone or sum of risperidone and 9-hydroxyrisperidone (Cp) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (Ce) and EEG effects, and the two limbs of hysteresis in the Cp-effect plot were collapsed in the Ce-effect plot for risperidone or risperidone plus 9-hydroxyrisperidone. CONCLUSION: The increases of absolute power for delta and theta frequency bands of EEG were induced by single oral administration of risperidone. The linear PK-PD model fit well with the relationship between effect compartment concentrations (Ce) and EEG effects of risperidone.

Administration, Oral↗
PubMed1982

Comparative effects of abrupt withdrawal of propranolol and verapamil in angina pectoris.

The potential hazards of abrupt withdrawal of propranolol have been described in patients with angina pectoris; however, the effects of abrupt withdrawal from long-term therapy with verapamil have not previously been investigated. The comparative effects of withdrawal from long-term treatment with propranolol and verapamil were assessed in a placebo-controlled double-blind randomized crossover study of 20 patients received placebo for 2 weeks, then increasing doses of propranolol (60 to 320 mg/day) or verapamil (240 to 480 mg/day) for 3 weeks. Patients were then abruptly withdrawn from drug onto placebo for 1 week, followed by crossover to the other drug treatment and a second withdrawal period. All 20 patients were withdrawn from verapamil without evidence of a rebound increase in frequency of anginal attacks, blood pressure, heart rate, or rate-pressure product and without a rebound deterioration in exercise tolerance. In contrast, with propranolol withdrawal, 2 patients (with the highest baseline angina attack rate) had a severe exacerbation of their anginal syndrome and could not undergo formal exercise testing; the other 18 patients were withdrawn from propranolol without incident. Plasma catecholamines were increased during exercise compared with rest during all treatments; however, the levels of catecholamines during exercise were significantly higher with propranolol than with verapamil and placebo (p less than 0.05). Levels of exercise catecholamines returned to placebo baseline values after withdrawal of propranolol.

Angina Pectoris↗
PubMed2006

Cognitive and memory effects of the new antiepileptic drugs.

Problems with cognition are common in patients with epilepsy. A series of double-blind, randomized, crossover, healthy volunteer studies have been conducted to avoid a variety of the confounding effects on cognition such as those produced by changes in seizure frequency. All of the older AEDs produced cognitive effects compared to the non-drug conditions. The cognitive effects of several of the new AEDs are described although data are limited. Studies have demonstrated that in utero AED exposure in humans may affect cognitive development. Although the cognitive effects of AEDs are generally modest, these effects can have clinical significance. The available data suggest that some of the new AEDs have fewer effects on cognition and memory than the older AEDs, and these differences can have clinical impact.

Animals↗