Setting: Community-based clinical research centers.Patients: Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase.Intervention: The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks.Main Outcome Measures: Primary outcome measures were adverse events, plasma and cerebrospinal fluid A␤ levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assess-ment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale.Results: Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups.Therewere3adverseevent-relateddiscontinuations, including 1 transient bowel obstruction. The plasma A␤ 40 concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (PϽ.001). No significant reductionwasseenincerebrospinalfluidA␤levels.Nogroup differences were seen in cognitive or functional measures.Conclusions: LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma A␤ concentrations were consistent with inhibition of ␥-secretase.

Progression from amnestic mild cognitive impairment to Alzheimer disease in this cohort was best determined by combining four common, easily administered, cognitive measures.

Multiple system atrophy (MSA) is a neurodegenerative disorder exhibiting a combination of parkinsonism, cerebellar ataxia, and autonomic failure. A disease-specific scale, the Unified Multiple System Atrophy Rating Scale (UMSARS), has been developed and validated to measure progression of MSA, but its use as an outcome measure for therapeutic trials has not been evaluated. On the basis of twelve months of follow-up from an observational study of 67 patients with probable MSA, we evaluated three disease-specific scores: Activities of Daily Living, Motor Examination, and a combined score from the UMSARS and two general health scores, the Physical Health and Mental Health scores of the SF-36 health survey, for their use as outcome measures in a therapeutic trial. We discuss related design issues and provide sample size estimates. Scores based on the disease-specific UMSARS seemed to be equal or superior to scores based on the SF-36 health survey. They appeared to capture disease progression, were well correlated and required the smallest sample size. The UMSARS Motor Examination score exhibited the most favorable characteristics as an outcome measure for a therapeutic trial in MSA with 1 year of follow-up.

Multislice 3DUS evaluation of the fetal face can be performed successfully with high image quality. This technique can be used to consistently and accurately differentiate the fetal primary palate and mandible. Fetuses with cleft lip with or without cleft palate can be identified with confidence.

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Poster abstractsand MCA Doppler flow patterns remained abnormal while the size of the DV became smaller. This suggests that the size of the DV is directly responsible for the shunting of umbilical venous away from the hepatic circulation. We postulate that the DV diameter is responsive to changes in oxygen tension in the fetal blood. P39.15The hyperoxygenation test shows persistent pulmonary vasoconstriction in fetuses with severe growth restriction D. C. Wood, J. C. Sabogal, J. Baxter, S. Weiner, V. Berghella Thomas Jefferson University, United StatesThe test for pulmonary vascular reactivity in the fetus compares changes in branch pulmonary artery Doppler flow patterns with the mother breathing room air with maternal hyperoxygenation. A normal response to oxygen is to increase the pulmonary flow patterns and is seen in fetuses greater than 30 weeks' gestation. Fetuses with severe growth restriction have redistribution of cardiac output to the brain, coronary and adrenal circulations. In fetuses greater than 30 weeks' gestation with absent or reversed diastolic flow in the free loop of the umbilical artery and increased diastolic flow in the middle cerebral artery, the pulsatility of the flow in the branch pulmonary artery did not change with maternal hyperoxygenation. This indicates a fixed pulmonary vasoconstriction similar to what is seen in fetuses with pulmonary hypoplasia, yet these fetuses had normal respiratory function for gestational age after delivery. In fifteen fetuses hospitalized for growth less than 10% of prediction for age with abnormal umbilical artery Doppler flow patterns, the hyperoxygenation test was offered to mothers after obtaining consent. The results from these studies were compared to 15 fetuses whose mothers were hospitalized for pre-eclampsia, premature rupture of the membranes and abruption. Those fetuses whose growth biometry was within normal limits had normal pulmonary vascular response to the maternal hyperoxygenation test while those with severe growth restriction did not. Of those fetuses who had received antenatal steroids prior to the hyperoxygenation test, there was no effect on pulmonary vasodilatation in those with severe growth restriction but those fetuses with normal growth appeared to have an exaggerated positive response. Objectives: To develop a technique utilizing multislice display to evaluate the fetal face and to assess its utility in the diagnosis of cleft lip and palate. Methods: 3D ultrasound volumes of the fetal face were acquired in 142 patients from January 2003 through November 2006. Of these, 15 patients had a confirmed diagnosis of cleft lip with or without cleft palate. Volumes were obtained by trained sonologists and reviewed by three readers on personal computer workstations. Volumes were manipulated so that orbits were made symmetrical; the cursor dot placed on the anterior aspect of the maxilla in the axial plane. Multislice function was activated with the maxilla as the reference slice and number of images set at nine. To determine the best int...