Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). Methods: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. Results: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p,0.001); adjusted OR = 2.97 (p,0.001)). There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate. A positive dose response for MCMs was found for lamotrigine (p = 0.006). Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate (OR = 2.49 (1.31 to 4.70)). Conclusions: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.

No abstract

Quasi-elastic light scattering has been used to study thermally excited capillary waves on free liquid surfaces over a considerably wider range of surface wavenumbers than hitherto. The surfaces of ethanol, water and of aqueous solutions of both ethanol and tertiary-butyl alcohol have been studied. The observed frequencies and damping constants of capillary waves of all wavenumbers are in good accord with theoretical predictions. For all liquids studied the surface tensions and viscosities deduced agreed with literature values to within 0.4 and 1.3% respectively. These results indicate that surface viscous effects postulated for water exist neither for that liquid nor for aqueous solutions of alcohols which are thought to enhance the inherent structure of water.

Objective-Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE.The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. Methods and Results-DSS was calculated using (mean diastolic velocityϫ8ϫblood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, Ϫ2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; PϽ0.001). DSS (dyne/cm 2 ) was significantly reduced in SLE patients (median, 18.5; range, 3.9 to 34.0 versus median 21.8; range, 14.1 to 58.7; Pϭ0.037). A strong correlation between FMD and DSS, r s ϭ0.65, Pϭ0.01 was found. Postischemic RI was not significantly different between the 2 groups; however, there were significant differences in the power-frequency spectrums of the Doppler velocity envelopes (PϽ0.05). Conclusions-These data suggest that in SLE, altered structure and function of the forearm microcirculation contributes to impaired FMD through a reduction in shear stress stimulus. Key Words: eigenvector Ⅲ flow-mediated dilation Ⅲ microcirculation Ⅲ shear stress Ⅲ systemic lupus erythematosus S ystemic lupus erythematosus (SLE) is the archetypal autoimmune disease, with a wide range of clinical manifestations. Among the clinical challenges of SLE, one of the most compelling is the high incidence of atherosclerosis in young women. In 1976, Urowitz et al showed a bimodal mortality pattern in SLE, with late deaths (comprising 45%) attributed to myocardial infarction. 1 Women with SLE have a high prevalence of coronary artery disease (CAD) 2 and an incidence of myocardial infarction up to 50 times higher than age-matched normals. 3 Classical risk factors are similar to those in the general population, 3 but the increased risk of atherosclerosis is not exclusively related to traditional Framingham risk factors alone, 4 with a recent report highlighting SLE itself as an independent risk. 5 Whereas several studies have highlighted the presence of subclinical atherosclerosis in SLE, 6,7 the pathogenesis is not fully understood. It has been proposed that autoimmune vascular injury in SLE may predispose to atherosclerotic plaque formation through mechanisms that promote endothelial dysfunction, the earliest precursor for plaque development. 8 -10 Flow-mediated dilation of the brachial artery (FMD) is used clinically as an indirect bioassay for endotheliumderived nitric oxide (NO) production. The primary hemodynamic determinant of FMD is wall shear stress, 11-13 and the degree of FMD has been shown to be proportional to both systolic and diastolic shear stress (DSS) in response to incr...

Glycerol mono-oleate monolayers at the air-water interface have been investigated by quasielastic light scattering from thermally excited capillary waves over a wide range of wave numbers. Using a relatively novel data analysis procedure four surface viscoelastic properties were deduced ab initio from the light scattering data : surface elastic moduli and viscosities governing shear normal to the monolayer (≡ tension) and dilation in the film plane. The tension and dilational modulus were compared with classical, equilibrium values in the first rigorous comparison of its kind. Various effects suggested that the two moduli were affected by rather different relaxation processes : discrepancies between the light scattering and equilibrium values of the two elastic moduli occurred in different states of the monolayer, and the two surface viscosities (both zero for the clean subphase) behaved very differently on monolayer compression. These effects were observed to be frequency dependent. In the fully compressed monolayer state the transverse shear modulus was characterised by an exponential relaxation, of time scale ∼ 9 μs. This relaxation time fell exponentially on monolayer expansion, reaching 100 ns for molecular areas ∼ 60 Å 2. Slower processes than these were rigorously excluded. The dilational modulus was generally less well determined than that affecting transverse shear. However in the expanded monolayer state, the data sufficed to demonstrate much slower relaxation, τ ∼ 290 μs. Possible molecular mechanisms are briefly discussed